[HN Gopher] Temozolomide Is Explosive
       ___________________________________________________________________
        
       Temozolomide Is Explosive
        
       Author : _Microft
       Score  : 135 points
       Date   : 2021-07-12 17:27 UTC (5 hours ago)
        
 (HTM) web link (blogs.sciencemag.org)
 (TXT) w3m dump (blogs.sciencemag.org)
        
       | cratermoon wrote:
       | As one comment there notes, just looking at all the Ns lined up
       | ought to cause concern, at least for anyone that has read this
       | authors "things I won't work with" series.
        
       | mcguire wrote:
       | " _You could say that TMZ is a prodrug for a prodrug for
       | methyldiazonium, which is never going to be a drug that can just
       | be administered by itself. ... temozolimide is genotoxic and
       | tetratogenic, so it has to be handled carefully, but honestly,
       | anything that generates a small diazonium compound so readily is
       | going to be similarly hazardous. ... Indeed, drop-hammer tests
       | showed that these TMZ samples decompose suddenly with smoke on
       | impact._ "
       | 
       | So, uh, what are the explosive decomposition products?
        
       | aazaa wrote:
       | The chemical structure is the clue to the explosive potential.
       | The N-N-N triad is a strange beast that shows up in a lot of
       | explosive materials. They're explosive for similar reasons that
       | ammonia nitrate is explosive.
       | 
       | https://www.newscientist.com/article/dn23399-texas-disaster-...
       | 
       | Think of energy as a vertical scale increasing upward. Including
       | a nitrogen triad (like in the drug) pushes the entire molecule up
       | on the energy scale. It's like riding the elevator to the 42nd
       | floor.
       | 
       | In contrast, the N-N triple bond (i.e., atmospheric nitrogen) is
       | way down at the ground floor. This is one reason that despite
       | nitrogen being the most abundant gas in the earth's atmosphere,
       | it requires large amounts of energy to process into fertilizers
       | and other materials.
       | 
       | CO2 and H2O also sit near ground level. So there's a large energy
       | difference between the drug and the combustion products N2, CO2,
       | and H2O.
       | 
       | All it takes to release all of that stored energy is a trigger.
       | For example, if someone were to push you off the top of the
       | building, you would spontaneously release the stored energy.
       | Hopefully you'd be equipped with an air braking device to
       | dissipate it gradually, but if not - well, that energy will be
       | released into your body and the pavement all at once.
        
       | gpvos wrote:
       | For those who don't know yet, Derek Lowe's series "Things I won't
       | work with" is very fun to read, and also educational.
       | https://blogs.sciencemag.org/pipeline/archives/category/thin...
        
       | meepmorp wrote:
       | Is it all that surprising though, considering how much nitrogen
       | is stuffed into that molecule?
        
       | lmilcin wrote:
       | I mean, seriously, just look at the molecule. All those nitrogen
       | atoms lying there restless to each go their own separate way:)
       | 
       | I would be surprised if it wasn't.
        
         | throwaway0a5e wrote:
         | At a bare minimum it'd probably be a damn good oxidizer at
         | which point you're 80% of the way to a good explosive.
        
           | [deleted]
        
         | mabbo wrote:
         | As someone who dropped chemistry in grade 11- what makes
         | Nitrogen so exciting like that?
         | 
         | So many common explosive compounds seem to have it.
        
           | jhallenworld wrote:
           | They can form molecules where nitrogen is not in its lowest
           | energy bond (which is the triple-bond N2 gas) and where a
           | reaction to this lower energy molecule can be triggered with
           | some small activation energy. The energy released provides
           | the activation energy for nearby material so you get a
           | chemical chain reaction.
        
           | G3rn0ti wrote:
           | Nitrogen-Nitrogen bonds inside larger molecules are never
           | quite stable because 1) nitrogen "wants" to form stable di-
           | nitrogen (N2) molecules containing a very stable triple bond
           | (an exothermic reaction) and 2) the result of such
           | decompositions is nitrogen gas increasing the amount of
           | entropy released (due to more molecules being created).
           | 
           | Reactions are driven both by the amount of heat released
           | (enthalpy) and the amount of "disorder" created (entropy).
           | Explosive reactions tend to be the ones where both factors
           | add to the driving force.
        
             | morpheuskafka wrote:
             | Does the same apply to oxygen? Since it also likes to be in
             | a diatomic form.
        
               | G3rn0ti wrote:
               | Oh, yes. Every substance carrying a ,,peroxo" in its name
               | is usually nasty stuff. Concentrated hydrogenperoxide for
               | example can explode creating gaseous water (aka steam)
               | and dioxygen (aka oxygen) in the process. While O2 is a
               | corrosive, it is quite inert under normal conditions
               | (which is why our clothes don't burst into flames
               | spontaneously).
        
               | masklinn wrote:
               | The opposite, or oxygen wouldn't be such a strong
               | oxidiser, which implies it readily and energetically
               | leaves its double bond behind for either single bonds
               | (H2O) or double bonds with non-oxygen atoms (CO2).
        
               | opportune wrote:
               | Diatomic oxygen is less stable than many other oxygen-
               | containing compounds like CO2 (that is why charcoal
               | burns) but diatomic nitrogen is pretty much as stable as
               | nitrogen can get.
        
               | lmilcin wrote:
               | Hydrogen peroxide at sufficient concentration can be used
               | as rocket fuel.
               | 
               | https://en.wikipedia.org/wiki/Hydrogen_peroxide
               | 
               | "High-concentration H2O2 is referred to as "high-test
               | peroxide" (HTP). It can be used either as a
               | monopropellant (not mixed with fuel) or as the oxidizer
               | component of a bipropellant rocket."
        
           | Thorondor wrote:
           | When nitrogen compounds combust, they tend to produce
           | nitrogen gas (N2). Since nitrogen molecules contain a very
           | strong nitrogen-nitrogen triple bond, a lot of energy is
           | released when they form.
        
           | jihadjihad wrote:
           | I thought this was an informative read for someone who also
           | only has a limited knowledge of chemistry:
           | 
           | https://wtamu.edu/~cbaird/sq/2013/06/27/when-does-the-
           | breaki...
        
         | short_sells_poo wrote:
         | I think some (many) blood vessel dilation meds are based on
         | nitroglycerin :)
         | 
         | https://en.wikipedia.org/wiki/Nitroglycerin_(medication)
         | 
         | I certainly remember looking with great suspicion at my
         | granddad's medicine and was very much disappointed when my
         | attempts to light his pills on fire did not yield rapid and
         | uncontrolled decomposition.
        
           | rzzzt wrote:
           | Wages of Fear, anyone? https://www.imdb.com/title/tt0046268/
        
       | dvirsky wrote:
       | That would have been a perfect device plot for Breaking Bad.
        
       | tyingq wrote:
       | Maybe helpful to note that the phrase "Class 1 Explosive" isn't
       | denoting a certain type, or power of "Explosive". "Class 1" in
       | Hazmat is all explosives. Class 2 is Gases. Class 3 is Flammable
       | or Combustible liquid, and so on.
        
         | Arrath wrote:
         | Fair point. The sub-classification gets into those weeds.
         | 
         | For example:
         | 
         | 1.1 being "mass explosion hazard", typically high-explosives.
         | 1.4 being "fire or projection hazard", typically consumer
         | fireworks, small arms ammunition. 1.5 is "may mass explode in
         | fire", things like AN fertilizer (Beirut; West, Texas), many
         | industrial blasting agents.
        
         | code_duck wrote:
         | So a liquor cabinet is full of Class 3 explosives.
        
         | MisterTea wrote:
         | Are you referring to the NFPA diamond?
         | https://en.wikipedia.org/wiki/NFPA_704
         | 
         | The explosive class mentioned is likely using a different scale
         | or standard.
        
           | tyingq wrote:
           | Pretty sure they are talking about Hazmat classes, where
           | "Class 1" is explosives.
           | 
           | See https://www.fmcsa.dot.gov/sites/fmcsa.dot.gov/files/docs/
           | Nin...
        
       | thewakalix wrote:
       | > tetratogenic
       | 
       | That's like a teratogen, but four times as bad!
        
         | gus_massa wrote:
         | Yep, it looks like a typo. Perhaps you can add a comment there
         | or send an email (it's available under his photo).
        
       | microtherion wrote:
       | Somewhat surprisingly, this was NOT filed under "Stuff I Won't
       | Work With"
        
         | wolfgang42 wrote:
         | Sounds like it got off on a technicality:
         | 
         |  _> I have personally worked with compounds that are this
         | hazardous, but at least I knew up front that they were!_
        
         | fabian2k wrote:
         | The stuff in that series is generally much more dangerous or
         | unusual in handling than this one.
        
         | ufmace wrote:
         | It sounds like this stuff is only mildly dangerous and easy to
         | keep safe with if you know what you're doing. Considering that
         | it's been used as a chemotherapy drug for years, it'd be
         | surprising if it wasn't.
         | 
         | Most of the "Stuff I Won't Work With" is fantastically
         | dangerous even when you know exactly what you're dealing with
         | and take all of the right precautions.
        
         | _Microft wrote:
         | If you had told me that the article was by Derek Lowe and that
         | there are a number of nitrogen atoms involved, I would have
         | indeed (wrongly) guessed that it were _Things I Won't Work
         | With_ , that the compound had been created by the Klapotke
         | group at Munich University and that it would go boom ;) Well,
         | not quite. This time at least.
        
       | wydfre wrote:
       | Well, the government is working on ways to deal with cancer[0].
       | 
       | [0]: https://www.irishtimes.com/news/voices-told-woman-she-had-
       | br...
        
       | olliej wrote:
       | I mean in fairness we still use nitroglycerine for some heart
       | ailments, so chemo - a field filled with horrific chemicals -
       | having an explosive shouldn't be too surprising.
        
         | wolfgang42 wrote:
         | The surprising part is that it's been around since the 1970s
         | and someone has only just gotten around to discovering this.
        
       | tyingq wrote:
       | Found the safety sheet for TMZ:
       | https://www.merck.com/docs/product/safety-data-sheets/hh-sds...
       | 
       | Nothing about explosions other than dust explosion warnings, but
       | this one is kind of amusing:
       | 
       |  _" H351 Suspected of causing cancer"_
        
         | cowboysauce wrote:
         | A lot of chemotherapy agents works by causing DNA damage and
         | are therefore carcinogenic themselves.
        
       | azinman2 wrote:
       | Chemotherapy is basically cave man medicine. That a therapeutic
       | drug is explosive only adds to that sentiment. The idea that
       | we'll basically poison you just up to a point that's nearly fatal
       | in order to kill the cancer is such a terrible way to treat
       | someone. Now I'm not saying don't ever do it -- unfortunately
       | that's where we're at in 2021. It's just kind of unbelievable
       | that cancer remains so elusive that we're still using medical
       | treatments that started from mustard gas usage during world wars,
       | when we're so advanced technologically in so many other ways.
       | 
       | Interestingly, cancers for children are largely successfully
       | treated. I was at a fancy conference a few years ago where some
       | cancer researchers were socializing over wine, and I asked them
       | why that was versus adults. They said the difference was that
       | parents are willing to do almost anything (aka enroll their kids
       | in experimental treatments) to cure their kids, but adults aren't
       | quite so willing for themselves. Thus the rate of experimentation
       | was just so much higher for children to the point where it's
       | often curable. Perhaps one day we'll be able to simulate the body
       | well enough to the point where we can brute force treatments
       | computationally to fix this gap.
        
         | 2OEH8eoCRo0 wrote:
         | >Perhaps one day we'll be able to simulate the body well enough
         | to the point where we can brute force treatments
         | computationally to fix this gap.
         | 
         | This is why as a total outsider/non-expert I believe we will
         | cure everything in the next 50 years if we do not regress or
         | destroy ourselves.
        
           | josefx wrote:
           | Remember how Steve Jobs suicided on fruitarianism instead of
           | getting his cancer treated when it was found in its early
           | stages? The biggest tech company on the planet was basically
           | led by an anti science lunatic with millions of followers.
           | 
           | We will probably end up almost destroying our selves twice
           | over before we get anywhere near curing every disease. On the
           | plus side wiping out almost all of humanity should also take
           | care of dozens of illnesses.
        
           | short_sells_poo wrote:
           | We still don't understand much of the inner workings of our
           | own body. It's a bit like the divide between quantum physics
           | and the macroscopic world. We have successfully observed and
           | modeled individual processes as they happen at a cellular
           | level, and we can draw some statistical conclusions at the
           | whole body level, but much of the area in-between is
           | basically unknown.
           | 
           | One just needs to look at nutrition or the farce that is
           | "nutrition science". We only barely understand what we are
           | supposed to eat to maximize our health, and that's such a
           | basic and fundamental concept that I feel anything like
           | "brute force treatments computationally to fix this gap."
           | would require multiple generational leaps in our
           | understanding. In other words, I feel like you are
           | extrapolating to space flight when we have just recently
           | invented the catapult.
           | 
           | Hell, we are only starting to suspect that the gut biome
           | affects our consciousness. How crazy is that? And yet it is a
           | very sobering indicator of how little we know. The human body
           | is an incredibly complicated system with so many feedback
           | loops that I'd put it in the same class as solving the
           | halting problem or establishing a grand unified theory of
           | physics.
           | 
           | We have modern robotics and tools like laser knives, but we
           | still have to poke needles into a patient's brain to
           | determine where to cut out tumors. I don't mean to disparage
           | the doubtlessly talented surgeons of today, but to me this
           | seems barely above medieval techniques. Our tools have
           | improved 100 fold, our understanding just barely.
           | 
           | I think _at best_ the prediction we can make is that  "we
           | believe eventually all diseases should be treatable". But to
           | say that in the next 50 years we can become functionally
           | immortal (treat all diseases), is a very long stretch IMO.
        
         | fabian2k wrote:
         | Many of the modern treatments are much more targeted, any
         | antibody-based treatment is by nature extremely specific. But
         | then you also have the problem that cancer isn't a single,
         | unified disease, so a very targeted approach doesn't work for
         | every cancer.
        
         | pcarolan wrote:
         | You're right that we haven't made much progress but this drug
         | is the only advancement in brain cancer in decades and has very
         | few side effects for most people. Compared to traditional
         | chemotherapy, it is a game changer for many patients' quality
         | of life.
        
         | caymanjim wrote:
         | Chemotherapy, like cancer, is not one thing. Some of it is a
         | matter of poisoning the body in ways that disrupt rapidly-
         | dividing cells. This is why chemo patients frequently lose
         | their hair (and other things you don't hear as much about, like
         | gametes, fingernails, mucous membranes/digestive lining). You
         | can call this "cave man medicine". Although that's more
         | dismissive than is warranted, there's no denying that it's a
         | blunt instrument.
         | 
         | Other chemotherapy treatments are "holy shit, we live in the
         | future." They're targeted and have almost no side effects.
         | 
         | You specifically reference mustard gas. I had lymphoma, and one
         | of my treatments was bendamustine, which is directly related to
         | that class of chemicals, and the subsequent research. It's
         | broadly toxic. The other treatment was rituximab, which is a
         | monoclonal antibody that targets the CD20 protein that
         | manifests on B cells, which are just one of many cells involved
         | in the lymphatic system.
         | 
         | I have to say the whole thing was a walk in the park.
         | Bendamustine isn't fun, but I never vomited once, never lost my
         | hair, and outwardly didn't look any different at all. I felt
         | pretty shitty for about three days once a month after
         | treatment. Kinda like a mild flu, but honestly I'd take the
         | bendamustine over the flu any day. I usually took three days
         | off work for it, primarily because I had to be at the chemo
         | infusion center for a few hours to get the drugs. I could have
         | worked through it (not that I should ever have had to, but I
         | could have). The rituximab was a walk in the park. I took that
         | once a month for a year, then every two months for two more
         | years. Aside from an allergic reaction the first time (solved
         | with Benadryl subsequently), I barely noticed it at all. It
         | was, at its worst, nowhere near as bad as a hangover.
         | 
         | I know I'm fortunate in that these treatments existed for my
         | cancer, and that my cancer has a high survival rate (I've been
         | clear for over a decade). Many people are far worse off, even
         | if they survive. I like to take these opportunities to dispel
         | some of the misconceptions that are out there.
        
         | vibrio wrote:
         | I agree with your wine-drinking physicians on clinical trial
         | participation, and your question on how to improve broader
         | participation. I also believe that there are fundamental
         | difference in cancers that arrive in a young person versus
         | cancers that have slowly evolved in the patients bodies,
         | perhaps over a decade or more-the latter are likely much more
         | stubborn.
        
         | dredmorbius wrote:
         | A rather surprising number of chemo compounds trace directly to
         | chemical warfare and compounds used during WWI, including
         | several mustard-gas-related compounds.
         | 
         | Some years ago, a close friend died of a relatively rare and
         | aggressive form of cancer. Among my roles was running
         | interference against those who were pitching various miracle
         | cures, with that tired old scam laetril playing a significant
         | role.
         | 
         | In the decades since, I've watched developments in the science
         | and development, as well as traced the history. It turns out
         | that the treatment received a few decades ago was little
         | changed from that of the 1960s, and has progressed little
         | since. Genetic sequencing identified the affected chromosome of
         | the triggering mutation in the 1980s, and we now know the
         | specific codons involved. There remains no cure.
         | 
         | Five year survival remains about 20%. Laetril is still a fraud.
         | And several of the other patients we came to know during the
         | course of my friend's treatment have died since of conditions
         | related to the treatment itself, though yes, they did buy
         | another 10--20 years.
         | 
         | Cancer is brutal.
         | 
         | I will note: "cancer" is a symptom cluster manifested by
         | malignant growth, and virtually always due to genetic mutation
         | within the affected cells (I'd say "always" though I'm not
         | completely sure of that). _The specific triggers, and the
         | possibilities for cure, vary tremendously._ Some bladder
         | cancers are virtually entirely treatable by, of all things,
         | tuberculosis baccili. Skin cancers if caught early pose little
         | risk. Others are tremendously aggressive, and an online friend
         | 's posts progressed from announcing their partner's diagnosis
         | with liver cancer to the partner's death over the course of
         | less than two months.
         | 
         | Broad-brush statements are virtually always false.
        
           | agumonkey wrote:
           | There's a weird wedding here, toxic/warfare compounds dropped
           | into your blood stream and nowadays it's used with
           | administrative processes (for repeatability and liability
           | purposes). Back in the days the people who came with the
           | chemotherapies were also aggressive in the way the approach
           | treatment (and according to De Vita it gave better results
           | [but maybe cost more])
        
             | dredmorbius wrote:
             | There's also a direct connection to vivisection and human-
             | subjects research during wartime which would fail to meet
             | most ethical review board standards today.
             | 
             | References are pretty easy to find:
             | 
             |  _After promising animal research, physician researchers
             | connected with Yale University and the University of
             | Chicago tried injecting sulfur mustard and its somewhat
             | milder relatives, the nitrogen mustards, into the veins of
             | cancer patients in the early 1940s. This was the first time
             | a systemic treatment was given for cancer. "It would upset
             | the whole body," says Smith. "That proved to be valuable
             | when you deal with certain kinds of leukemia or lymphoma."_
             | 
             | https://www.the-scientist.com/foundations/from-chemical-
             | weap...
             | 
             |  _Not long after the discovery of nitrogen mustard, Sidney
             | Farber of Boston demonstrated that aminopterin, a compound
             | related to the vitamin folic acid, produced remissions in
             | children with acute leukemia._
             | 
             | https://www.cancer.org/cancer/cancer-basics/history-of-
             | cance...
             | 
             | I'm not certain Japan's Unit 731 was engaged in research
             | with chemotherapy precursors, though the range of testing
             | was extensive, and the US provided a grant of immunity
             | after the war.
             | 
             | Please note that pretty much anything horrific you can
             | imagine, and then some, is discussed in the links which
             | follow.
             | 
             | https://nationalinterest.org/blog/reboot/unit-731-japans-
             | sec...
             | 
             | https://en.wikipedia.org/wiki/Unit_731
        
         | devy wrote:
         | I am not surprised the a Class 1 HAZMAT is used as the chemo
         | agent for glioblastoma, the most malignant form of brain tumor.
         | My father in law just recently passed with glioblastoma stage
         | 3, from admitted to hospital to passing in a couple of month.
        
         | robbiep wrote:
         | The cancers that are treated successfully in children are the
         | blood borne ones (mostly leukemias) and generally because
         | they're easier to wipe out and replace the marrow with. Some
         | Childhood brain tumours are also very successfully treated, and
         | most other adult cancers children don't get. Sarcomas still
         | kill people left right and centre though.
         | 
         | The truth is that we're already peeking out of the dark ages of
         | chemotherapy. Immunotherapies have revolutionised the field and
         | new stuff coming online is incredible. When I started medical
         | school 11 years ago the 5 year survival of metastatic melanoma
         | was close to 0%. It's now close to the population average
         | (well, not really, but it's greater than 50%). Records are
         | being smashed
        
           | et2o wrote:
           | Metastatic melanoma? I haven't seen any data showing close to
           | 50% survival rate, where are you looking? Just managed a
           | young patient with metastatic melanoma and very poor
           | prognosis.
        
             | Herodotus38 wrote:
             | I think they were referring to pd-1 inhibitors. I'm not an
             | oncologist but that generally fits with what I've seen as a
             | hospitalist. FWIW I personally know someone who has
             | survived > 5 years who received it right when it cane out.
             | 
             | Here's a paper supporting:
             | 
             | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019511/
        
               | jcims wrote:
               | PD-1 inhibitors seem like magic when they work.
               | 
               | Unfortunately they don't work in every case, but it's
               | abundantly clear when they do that the immune system is
               | good at killing unwanted cells roaming around the body.
               | *smacks forehead*
        
             | robbiep wrote:
             | Yes sorry I should have specified, PD-1s. Was 4am in
             | australia on mobile and wasn't in the mood to reference.
             | Sorry
        
         | cubicmeter wrote:
         | this could be true that as a different example along the lines
         | of the same conclusion: Women-only medical conditions are less
         | known by medical fields, and there are fewer treatments. Its
         | because the society treats women's lives less seriously. For
         | example pregnancy is still pretty mysterious in general
         | medicine. Birth control pills are to prevent women fertility
         | etc. It could be true that children lives are deemed more
         | important by parents and more researched.
        
         | open-source-ux wrote:
         | My understanding is that chemotherapy is indiscrimate when it
         | attacks cells - it affects cancerous and healthy cells alike.
         | However, doctors assume the healthy cells will recover from the
         | weakening effects of chemotherapy. Meanwhile the cancer cells
         | are stressed to a greater degree by the chemotherapy and thus
         | suspectible to death. All this is presented as the "best
         | outcome" scenario for chemotherapy treament.
         | 
         | However, for some patients (and depending on their type of
         | cancer) chemotheraphy can leave lingering side-effects and can
         | even cause cancerous cells to recur or turn even more
         | aggressive. For some cancer patients, chemotherapy is not about
         | curing the cancer but slowing the cancer spread ("treatable but
         | not curable" is the phrase used by doctors for some cancer
         | conditions).
         | 
         | Although chemotheraphy can be succesful for some (many?)
         | patients, as you say it still feels like a crude, blunt
         | approach to treating cancer. Doctors might baulk at that
         | description. But consider: if someone has a non-metasized
         | cancer (i.e. cancer in one part of the body that has not spread
         | to other parts of the body), chemotherapy is applied with blunt
         | force to the entire body including to the majority of healthy
         | cells in the body. I can't see how anyone can say this isn't a
         | coarse and crude treatment method even when the outcome is
         | deemed successful.
        
           | zaroth wrote:
           | Not entirely indiscriminate. For example as I understand it,
           | a lot of chemo drugs attack cells that divide quickly. Which
           | is why a lot of times hair loss is a side effect because they
           | are some of the faster dividing cells in the body.
        
             | da_chicken wrote:
             | My understanding was that chemotherapy drugs often affect
             | cells literally _as they divide_. The exact mechanisms
             | vary, but it 's that timing of affecting a cell during
             | division that makes a given substance possible to be used
             | as chemotherapy drug.
        
         | joe_the_user wrote:
         | Chemotherapy combined with surgery and radiation is still a
         | standard and still does cure a significant portion of people -
         | my father's cancer was cured by this "ordinary method".
         | 
         | The problem is that more selective methods of killing cancers
         | run up against the tendency of cancer cells to mutate and find
         | a defense against them.
         | 
         | And this is definitely stuff that's killing you and the cancer
         | and hoping the cancer dies first. To keep going, you need a
         | strong reason to live.
        
         | gus_massa wrote:
         | > _That a therapeutic drug is explosive only adds to that
         | sentiment._
         | 
         | Explosivity and toxicity are unrelated. Cyanide can kill you,
         | but it's not explosive IIRC. You can make explosives with
         | aluminum, but it's safe to use as a food container, ...
         | 
         | > _Chemotherapy is basically cave man medicine._
         | 
         | The main problem is that cancer cells and normal cells are very
         | similar. Anything that kills cancer cells will probably kill
         | normal cells. Anything that is safe for normal cells is
         | probably safe for cancer cells. Killing one but not the other
         | is like a poll trickshot.
         | 
         | (Killing bacteria or fungus is easier, because some of the
         | molecules they use are different, and sometimes they produce
         | the molecules using a different method, so you can make a drug
         | that attack the difference and hope the best.)
         | 
         | Also, not all the treatment for cancer use chemotherapy
         | methods. Some cancers are affected by hormones, so you can
         | modify the hormone levels. (This also cause problems in the
         | part of you body that use the hormone, so it's a tradeoff.)
        
       | ashtonkem wrote:
       | Kind of surprising nobody thought to check until now. Even as a
       | non chemist (albeit a regular reader of Derek Lowe), I look at
       | that and say "boy is that a lot of nitrogens, I wonder if they're
       | itching to become an expanding cloud of hot nitrogen gas and
       | broken lab equipment".
        
       | languagehacker wrote:
       | Reminds me of how DNP, a chemical used for creating explosives,
       | has been used as a weight-loss drug. It's surprisingly effective,
       | but overdosing on it will result in a long, hot, agonizing death.
        
         | southeastern wrote:
         | DNP was banned after causing a lot of deaths. Still a
         | fascinating drug, I don't remember exactly how it worked but it
         | disrupted respiration so that less ATP was produced from
         | electrons while their energy instead was 'spent' increasing
         | heat
        
           | bserge wrote:
           | So has Clenbuterol (pure stimulant), Sibutramine (an ADHD
           | medication way before its time, marketed as a weight loss
           | drug by some idiot marketers), and many others.
           | 
           | Really should stop banning drugs because a few morons
           | overdosed on them.
           | 
           | I mean, no one has banned stairs yet. They tried to ban
           | alcohol, but the conviction turned out paper thin.
           | 
           | I guess it is easier to ban something that only benefits a
           | sad small minority. Bonus evil points when the rich can get
           | the drug regardless.
        
         | G3rn0ti wrote:
         | The fundamental reason why 2,4-Dinitrophenol (DNP) burns fat is
         | surprisingly complicated. Basically, it intoxicates
         | mitochondria in your cells being their power houses. These
         | organelles create ATP, a universal metabolic energy carrier, by
         | maintaining a proton gradient across its membrane. By means of
         | chemical osmosis this gradient is what drives the ATP synthase
         | enzyme under normal conditions. Now, DNP is capable of
         | shuttling protons along the gradient and short-circuits this
         | process catalyzing the conversion of fatty acids into worthless
         | heat.
         | 
         | Interestingly, babies use a controlled variant of this
         | mechanism to help maintain their body temperature thanks to
         | their brown fat tissue. It makes babies look cute and keep
         | warm. :)
        
           | jcims wrote:
           | This is an animation and cursory explanation of ATP
           | synthesis, with suitably dramatic music:
           | 
           | https://www.youtube.com/watch?v=OT5AXGS1aL8
           | 
           | This animation and associated narration is much more
           | detailed, but a bit slow for something you haven't vetted
           | your interest in yet :)
           | 
           | https://www.youtube.com/watch?v=kXpzp4RDGJI
        
       | dylan604 wrote:
       | "What they found was rapid onset of decomposition at 170 degrees"
       | 
       | So this seems to be more about people in a lab situation rather
       | than it being so unstable it reacting sitting in someone's hot
       | car.
       | 
       | Suspecting it to react at 212 and finding it reacting at 170
       | could ruin a lab tech's day to be sure. Those are the jobs that
       | sound fun "for the science" lets see what happens when...
        
         | LeifCarrotson wrote:
         | "Decomposition" doesn't usually mean 'explodes', either.
         | 
         | Curiously, Wikipedia still shows the old definition [1]:
         | 
         | > _Temozolomide is an imidazotetrazine derivative. It is
         | slightly soluble in water and aqueous acids, and decomposes at
         | 212 degC (414 degF).[15]_
         | 
         | The [15] citation from Wikipedia is to a 1982 book,
         | untranslated from German. That may be one example of "the
         | literature" that Derek cites. The factoid was added in this
         | edit [2] by an Austrian Wikipedia editor who works on a lot of
         | chemistry articles. I'd wager that the number of people who are
         | English-German bilingual chemists with this book from 1982 on
         | their shelf who edit Wikipedia is exactly one, and further,
         | that he did not experimentally test or have other familiarity
         | with the compound to sanity check the fact. This puts "the
         | literature" in a very different context than the broad
         | consensus of well-known, agreed-upon facts that I'd usually
         | assume a constant value to have.
         | 
         | [1]:
         | https://en.wikipedia.org/wiki/Temozolomide#Chemical_properti...
         | 
         | [15]: Dinnendahl, V; Fricke, U, eds. (2016). Arzneistoff-
         | Profile (in German). 9 (29 ed.). Eschborn, Germany: Govi
         | Pharmazeutischer Verlag. ISBN 978-3-7741-9846-3.
         | 
         | [2]:
         | https://en.wikipedia.org/w/index.php?title=Temozolomide&diff...
        
         | cratermoon wrote:
         | Something about that part of the article had me wondering. It
         | seems they ran some sophisticated tests to determine the
         | physical properties which would lead to it decomposing, but
         | they didn't actually put a sample of the stuff on a source in a
         | vent hood? It does say they later ran some standard tests for
         | explosivity on it, I suppose that counts?
        
         | munificent wrote:
         | I think you're overlooking the most important scenario: mass
         | production of it in a factory setting.
        
           | dylan604 wrote:
           | I think that falls under my qualification of "people in a lab
           | setting"
        
           | ISL wrote:
           | And just handling/storage. Things that are flammable or
           | explosive have more-stringent requirements.
           | 
           | A familiar example: one should take much greater care when
           | storing rubbing alcohol (or Bacardi 151 or vodka) than wine.
           | One will magnify a house-fire. The other will help to douse a
           | flame.
        
             | laurent92 wrote:
             | At every people's house, I see a cupboard with the
             | chemicals. WD-40, 90deg alcohol, acetone, white spirit, all
             | in the same IKEA (=plywood) cupboard (although it would be
             | hard to protect children if they were each in a different
             | cupboard too). I wonder how many fires start from the
             | chemicals cupboard. We know that a lot of artists had their
             | rag pile spontaneously heating up then catching fire...
        
               | throwawayboise wrote:
               | Those things are fine in their separate containers. They
               | will not spontaneously combust. If the containers are
               | leaking, or fire starts elsewhere, yeah they could become
               | fuel. But really no more than any other hydrocarbons in
               | your house (e.g. wood, plastic, cloth, upholstrey and
               | foam cushions, etc.)
        
               | munificent wrote:
               | _> They will not spontaneously combust._
               | 
               | Linseed oil or other drying oils can if they have enough
               | exposure to air.
               | 
               | A couple years ago, my wife re-oiled our wooden patio
               | furniture and threw all the paper towels in the trash.
               | Ten minutes later, smoke was pouring out of the trash
               | can. Fortunately, I managed to get it out of the house
               | before the fire spread.
        
               | cratermoon wrote:
               | In case of fire, does it matter that they are all in one
               | cabinet together? Should they be stored separately so
               | that a fire that does reach one won't cause a serious
               | acceleration through combinations?
        
             | cratermoon wrote:
             | See, for example, Beirut.
        
         | lflux wrote:
         | nb: Decomposition happens at 170 degrees _Celsius_ - around 340
         | degrees Fahrenheit. A fair bit warmer than a hot car usually
         | gets.
        
         | manmal wrote:
         | Fires can start anywhere, and a small explosion can make the
         | difference between the firefighters arrive on time vs the
         | building burns down and people die.
        
           | dylan604 wrote:
           | Or the firefighters getting killed in the explosion because
           | something blew up 45 degrees early than expected.
           | 
           | All sorts of things can go wrong when things react at
           | unexpected times. Are we really going to attempt to list all
           | of them? It'll be a long list of replies.
        
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