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Chlormethine

January 01, 1970

Not to be confused with Chloromethane.

Chlormethine (INN, BAN), also known as mechlorethamine (USAN, USP), mustine, HN2, and (in post-Soviet states) embikhin (эмбихин), is a nitrogen mustard sold under the brand name Mustargen among others. It is the prototype of alkylating agents, a group of anticancer chemotherapeutic drugs. It works by binding to DNA, crosslinking two strands and preventing cell duplication. It binds to the N7 nitrogen on the DNA base guanine. As the chemical is a blister agent, its use is strongly restricted within the Chemical Weapons Convention where it is classified as a Schedule 1 substance.

Chlormethine
Names
IUPAC name
2-Chloro-N-(2-chloroethyl)-N-methylethanamine
Other names
  • Bis(2-chloroethyl)(methyl)amine
  • mechlorethamine
  • mustine
  • HN-2
  • Ledaga[1][2]
Identifiers
  • 51-75-2 Y
3D model (JSmol)
  • Interactive image
ChEBI
  • CHEBI:28925 Y
ChEMBL
  • ChEMBL427 Y
ChemSpider
  • 3893 Y
DrugBank
  • DB00888 Y
ECHA InfoCard 100.000.110
EC Number
  • 200-120-5
KEGG
  • D0767 N
MeSH Mechlorethamine
  • 4033
RTECS number
  • IA1750000
UNII
  • 50D9XSG0VR Y
UN number 2810
  • DTXSID2020975
  • InChI=1S/C5H11Cl2N/c1-8(4-2-6)5-3-7/h2-5H2,1H3 Y
    Key: HAWPXGHAZFHHAD-UHFFFAOYSA-N Y
  • CN(CCCl)CCCl
Properties
C5H11Cl2N
Molar mass 156.05 g·mol−1
Appearance Colorless liquid
Odor Fishy, ammoniacal
log P 0.91
Pharmacology
D08AX04 (WHO) L01AA05 (WHO)
  • Intracavitary
  • Intrapericardial
  • Intravenous
  • Topical
Pharmacokinetics:
<1 minute
50% (Kidney)
Legal status
Related compounds
Related amines
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
N verify (what is YN ?)

Mechlorethamine belongs to the group of nitrogen mustard alkylating agents.[4][5][6]

Uses edit

It has been derivatized into the estrogen analogue estramustine phosphate, used to treat prostate cancer. It can also be used in chemical warfare where it has the code-name HN2. This chemical is a form of nitrogen mustard gas and a powerful vesicant. Historically, some uses of mechlorethamine have included lymphoid malignancies such as Hodgkin's disease, lymphosarcoma, chronic myelocytic leukemia, polycythemia vera, and bronchogenic carcinoma [7] Mechlorethamine is often administered intravenously,[8] but when compounded into a topical formulation it can also be used to treat skin diseases. There have been studies demonstrating that topical administration of mechlorethamine has efficacy in mycosis fungoides-type cutaneous T cell lymphoma.[9][10][11]

Another use of chlormethine is in the synthesis of pethidine (meperidine).[12]

Side effects and toxicity edit

Mechlorethamine is a highly toxic medication, especially for women who are pregnant, breastfeeding, or of childbearing age.[13][14] At high enough levels, exposure can be fatal.[6]

The adverse effects of mechlorethamine depend on the formulation.[15] When used in chemical warfare, it can cause immunosuppression and damage to mucous membranes of the eyes, skin, and respiratory tract. Mucous membranes and damp or damaged skin are more affected by exposure to HN-2. Though symptoms of exposure are generally delayed, the DNA damage it causes occurs very quickly. More serious exposures cause symptoms to develop sooner. Eye symptoms develop first, in the first 1–2 hours (severe exposure) or 3–12 hours (mild to moderate exposure) followed by airway (2-6/12–24 hours) and skin symptoms (6–48 hours). Hot, humid weather shortens the latent (symptom-free) period.[6]

Symptoms of toxic exposure to HN-2 vary based on the route of exposure. Eye exposure causes lacrimation (tear production), burning, irritation, itching, a feeling of grittiness or dryness, blepharospasm (spasms of the eyelid), and miosis (pinpoint pupils). More severe cases cause edema (swelling from fluid accumulation) in the eyelids, photophobia (extreme sensitivity to light), severe pain, corneal ulceration, and blindness.[6]

Inhalation of chlormethine damages the upper and lower airways sequentially, with more severe exposures causing faster damage that afflicts lower parts of the respiratory tract. Early symptoms include rhinorrhea (runny nose), epistaxis (nosebleed), toneless voice, sneezing, barking cough, and dyspnea (in smokers and asthmatics). Later symptoms include pain in the nose/sinuses and inflammation of the airway. In severe cases, there may be epithelial necrosis throughout the respiratory tract, causing pseudomembrane formation, which can obstruct the airway. Pneumonia may develop and prove fatal.[6]

Skin exposure mainly causes erythema (redness) and vesication (blistering) at first, but absorption through the skin causes systemic toxicity. In cases where more than 25% of the skin is affected, fatal exposure is likely to have occurred.[6]

Though ingestion is uncommon, if mechlorethamine is swallowed it causes severe chemical burns to the gastrointestinal tract and concomitant nausea, vomiting, diarrhea, abdominal pain, and hemorrhage.[6]

Long-term effects of acute or chronic chlormethine exposure are caused by damage to the immune system. White blood cell counts drop, increasing the risk of infection, and red blood cell and platelet counts may also drop due to bone marrow damage. Chronic eye infections may result from exposure, but blindness is temporary. Long-term effects on the respiratory system include anosmia (inability to smell), ageusia (inability to taste), inflammation, chronic infections, fibrosis, and cancer. Skin that has been damaged by HN2 can change pigmentation or become scarred, and may eventually develop cancer.[6]

History edit

The effect of vesicant (blister) agents in the form of mustard gas (sulfur mustard, Bis(2-chloroethyl) sulfide) on bone marrow and white blood cells had been known since the First World War.[16] In 1935 several lines of chemical and biological research yielded results that would be explored after the start of the Second World War. The vesicant action of a family of chemicals related to the sulfur mustards, but with nitrogen substituting for sulfur was discovered—the "nitrogen mustards" were born.[17] The particular nitrogen mustard chlormethine (mechlorethamine) was first synthesized.[18] And the action of sulfur mustard on tumors in laboratory animals was investigated for the first time.[19]

After the US entry into the Second World War the nitrogen mustards were candidate chemical warfare agents and research on them was initiated by the Office of Scientific Research and Development (OSRD). The OSRD let contracts to study them to two universities—Yale University and the University of Chicago. Inspired perhaps by the preliminary research in 1935, independently both groups thought to test whether a medically useful differential toxicity between animals and animal tumors existed.[20] The Yale pharmacologists Louis Goodman and Alfred Gilman were the first to conduct a clinical trial, on 27 August 1942, using the agent HN3 (tris(2-chloroethyl)amine) on a patient known as J.D.[21][22][23]

The next year the Chicago group, led by Leon O. Jacobson, conducted trials with HN2 (chlormethine) which was the only agent in this group to see eventual clinical use. Wartime secrecy prevented any of this ground-breaking work on chemotherapy from being published, but papers were released once wartime secrecy ended, in 1946.[24]

Chemistry edit

Chlormethine is combustible and becomes explosive under extreme conditions. It can react with metals to form gaseous hydrogen.[6]

References edit

  1. ^ a b c "Ledaga". Therapeutic Goods Administration (TGA). 30 June 2021. from the original on 5 September 2021. Retrieved 5 September 2021.
  2. ^ a b "Ledaga EPAR". European Medicines Agency. 17 September 2018. from the original on 5 September 2021. Retrieved 5 September 2021.
  3. ^ "Health product highlights 2021: Annexes of products approved in 2021". Health Canada. 3 August 2022. Retrieved 25 March 2024.
  4. ^ Rappeneau S, Baeza-Squiban A, Jeulin C, Marano F (March 2000). "Protection from cytotoxic effects induced by the nitrogen mustard mechlorethamine on human bronchial epithelial cells in vitro". Toxicol. Sci. 54 (1): 212–21. doi:10.1093/toxsci/54.1.212. PMID 10746948.
  5. ^ "Chapter 3: Principles of Oncologic Pharmacotherapy". . 2010. Archived from the original on 15 May 2009. Retrieved 8 October 2023.
  6. ^ a b c d e f g h i "CDC - The Emergency Response Safety and Health Database: Blister Agent: NITROGEN MUSTARD HN-2 - NIOSH". U.S. Centers for Disease Control and Prevention (CDC). from the original on 2019-06-28. Retrieved 2016-04-20.
  7. ^ Bunn Jr, P. A.; Hoffman, S. J.; Norris, D; Golitz, L. E.; Aeling, J. L. (1994). "Systemic therapy of cutaneous T-cell lymphomas (mycosis fungoides and the Sézary syndrome)". Annals of Internal Medicine. 121 (8): 592–602. doi:10.7326/0003-4819-121-8-199410150-00007. PMID 8085692. S2CID 22909007.
  8. ^ Medline (2012). Mechlorethamine. Retrieved from https://www.nlm.nih.gov/medlineplus/druginfo/meds/a682223.html 2016-07-05 at the Wayback Machine
  9. ^ Lindahl LM, Fenger-Gron M, Iversen L. Topical nitrogen mustard therapy in patients with mycosis fungoides or parapsoriasis. J Eur Acad Dermatol Venereol. 2013 Feb;27(2):163-8.
  10. ^ Galper SL, Smith BD, Wilson LD. Diagnosis and management of mycosis fungoides. Oncology (Williston Park). 2010 May;24(6):491-501.
  11. ^ Lessin SR, Duvic M, Guitart J, Pandya AG, Strober BE, Olsen EA, Hull CM, Knobler EH, Rook AH, Kim EJ, Naylor MF, Adelson DM, Kimball AB, Wood GS, Sundram U, Wu H, Kim YH. Topical chemotherapy in cutaneous T-cell lymphoma: positive results of a randomized, controlled, multicenter trial testing the efficacy and safety of a novel mechlorethamine, 0.02%, gel in mycosis fungoides. JAMA Dermatol. 2013 Jan;149(1):25-32.
  12. ^ McErlane, KM; Wood, RJ; Matsui, F; Lovering, EG (July 1978). "Impurities in Drugs II: Meperidine and Its Formulations". Journal of Pharmaceutical Sciences. 67 (7): 958–961. doi:10.1002/jps.2600670723. PMID 660515.
  13. ^ Recordati Rare Diseases Inc. (2013). Mustargen Package Insert. Retrieved from https://www.drugs.com/pro/mustargen.html 2018-09-20 at the Wayback Machine
  14. ^ Actelion Pharmaceuticals Ltd. (2013) Valchlor Package Insert. Retrieved from http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/202317lbl.pdf 2021-03-28 at the Wayback Machine
  15. ^ Mustargen 2018-09-20 at the Wayback Machine and Valchlor 2021-03-28 at the Wayback Machine
  16. ^ Krumbhaar EB, Krumbhaar HD (1919). "The blood and bone marrow in yellow cross gas (mustard gas) poisoning: changes produced in the bone marrow of fatal cases". J Med Res. 40 (5): 497–508. doi:10.1016/0002-9610(63)90232-0. PMID 13947966. from the original on 2020-02-10. Retrieved 2018-10-14.
  17. ^ Ward, Kyle (1935). "The Chlorinated Ethylamines — A New Type of Vesicant". J. Am. Chem. Soc. 57 (5): 914–916. doi:10.1021/ja01308a041.
  18. ^ V. Prelog, V. Štěpán (1935). "Nouvele synthèse des pipérazines N-monoalcoylées (VIIième communication sur les bis-[β-halogénoéthyl]-amines)". Collection of Czechoslovak Chemical Communications. 7: 93–102. doi:10.1135/cccc19350093.
  19. ^ Berenblum I. (1935). "Experimental inhibition of tumor induction by mustard gas and other compounds". Journal of Pathology and Bacteriology. 40 (3): 549–558. doi:10.1002/path.1700400312.
  20. ^ Einhorn, J. (1985). "Nitrogen mustard: the origin of chemotherapy for cancer". Int J Radiat Oncol Biol Phys. 11 (7): 1375–1378. doi:10.1016/0360-3016(85)90254-8. PMID 3891698.
  21. ^ Alfred Gilman, Frederick S. Philips (1946). "The Biological Actions and Therapeutic Applications of the B-Chloroethyl Amines and Sulfides". Science. 103 (2675): 409–436. Bibcode:1946Sci...103..409G. doi:10.1126/science.103.2675.409. PMID 17751251.
  22. ^ Gilman, Alfred (1963). "The initial clinical trial of nitrogen mustard". Am J Surg. 105 (5): 574–578. doi:10.1016/0002-9610(63)90232-0. PMID 13947966.
  23. ^ Fenn, John E.; et al. (2011). "First Use of Intravenous Chemotherapy Cancer Treatment: Rectifying the Record". Journal of the American College of Surgeons. 212 (3): 413–417. doi:10.1016/j.jamcollsurg.2010.10.018. PMID 21247779.
  24. ^ Jacobson L.O., Spurr C.L., Barron E., Smith T., Lushbaugh C., Dick G.F. (1946). "Nitrogen Mustard Therapy: Studies on the Effect of Methyl-Bis (Beta-Chloroethyl) Amine Hydrochloride on Neoplastic Diseases and Allied Disorders of the Hemopoietic System". JAMA. 132 (2675): 263–271. doi:10.1001/jama.1946.02870400011003. PMID 20997209.{{cite journal}}: CS1 maint: multiple names: authors list (link)

January 01, 1970
chlormethine, confused, with, chloromethane, also, known, mechlorethamine, usan, mustine, post, soviet, states, embikhin, эмбихин, nitrogen, mustard, sold, under, brand, name, mustargen, among, others, prototype, alkylating, agents, group, anticancer, chemothe. Not to be confused with Chloromethane Chlormethine INN BAN also known as mechlorethamine USAN USP mustine HN2 and in post Soviet states embikhin embihin is a nitrogen mustard sold under the brand name Mustargen among others It is the prototype of alkylating agents a group of anticancer chemotherapeutic drugs It works by binding to DNA crosslinking two strands and preventing cell duplication It binds to the N7 nitrogen on the DNA base guanine As the chemical is a blister agent its use is strongly restricted within the Chemical Weapons Convention where it is classified as a Schedule 1 substance Chlormethine Names IUPAC name 2 Chloro N 2 chloroethyl N methylethanamine Other names Bis 2 chloroethyl methyl aminemechlorethaminemustineHN 2Ledaga 1 2 Identifiers CAS Number 51 75 2 Y 3D model JSmol Interactive image ChEBI CHEBI 28925 Y ChEMBL ChEMBL427 Y ChemSpider 3893 Y DrugBank DB00888 Y ECHA InfoCard 100 000 110 EC Number 200 120 5 KEGG D0767 N MeSH Mechlorethamine PubChem CID 4033 RTECS number IA1750000 UNII 50D9XSG0VR Y UN number 2810 CompTox Dashboard EPA DTXSID2020975 InChI InChI 1S C5H11Cl2N c1 8 4 2 6 5 3 7 h2 5H2 1H3 YKey HAWPXGHAZFHHAD UHFFFAOYSA N Y SMILES CN CCCl CCCl Properties Chemical formula C 5H 11Cl 2N Molar mass 156 05 g mol 1 Appearance Colorless liquid Odor Fishy ammoniacal log P 0 91 Pharmacology ATC code D08AX04 WHO L01AA05 WHO Pregnancycategory AU B3 1 Routes ofadministration IntracavitaryIntrapericardialIntravenousTopical Pharmacokinetics Biological half life lt 1 minute Excretion 50 Kidney Legal status AU S4 Prescription only 1 CA only 3 EU Rx only 2 In general Prescription only Related compounds Related amines DimethylamineTrimethylamineN NitrosodimethylamineDiethylamineTriethylamineDiisopropylamineDimethylaminopropylamineDiethylenetriamineN N DiisopropylethylamineTriisopropylamineTris 2 aminoethyl amineHN1 nitrogen mustard HN3 nitrogen mustard Except where otherwise noted data are given for materials in their standard state at 25 C 77 F 100 kPa N verify what is Y N Infobox references Mechlorethamine belongs to the group of nitrogen mustard alkylating agents 4 5 6 Contents 1 Uses 2 Side effects and toxicity 3 History 4 Chemistry 5 ReferencesUses editIt has been derivatized into the estrogen analogue estramustine phosphate used to treat prostate cancer It can also be used in chemical warfare where it has the code name HN2 This chemical is a form of nitrogen mustard gas and a powerful vesicant Historically some uses of mechlorethamine have included lymphoid malignancies such as Hodgkin s disease lymphosarcoma chronic myelocytic leukemia polycythemia vera and bronchogenic carcinoma 7 Mechlorethamine is often administered intravenously 8 but when compounded into a topical formulation it can also be used to treat skin diseases There have been studies demonstrating that topical administration of mechlorethamine has efficacy in mycosis fungoides type cutaneous T cell lymphoma 9 10 11 Another use of chlormethine is in the synthesis of pethidine meperidine 12 Side effects and toxicity editMechlorethamine is a highly toxic medication especially for women who are pregnant breastfeeding or of childbearing age 13 14 At high enough levels exposure can be fatal 6 The adverse effects of mechlorethamine depend on the formulation 15 When used in chemical warfare it can cause immunosuppression and damage to mucous membranes of the eyes skin and respiratory tract Mucous membranes and damp or damaged skin are more affected by exposure to HN 2 Though symptoms of exposure are generally delayed the DNA damage it causes occurs very quickly More serious exposures cause symptoms to develop sooner Eye symptoms develop first in the first 1 2 hours severe exposure or 3 12 hours mild to moderate exposure followed by airway 2 6 12 24 hours and skin symptoms 6 48 hours Hot humid weather shortens the latent symptom free period 6 Symptoms of toxic exposure to HN 2 vary based on the route of exposure Eye exposure causes lacrimation tear production burning irritation itching a feeling of grittiness or dryness blepharospasm spasms of the eyelid and miosis pinpoint pupils More severe cases cause edema swelling from fluid accumulation in the eyelids photophobia extreme sensitivity to light severe pain corneal ulceration and blindness 6 Inhalation of chlormethine damages the upper and lower airways sequentially with more severe exposures causing faster damage that afflicts lower parts of the respiratory tract Early symptoms include rhinorrhea runny nose epistaxis nosebleed toneless voice sneezing barking cough and dyspnea in smokers and asthmatics Later symptoms include pain in the nose sinuses and inflammation of the airway In severe cases there may be epithelial necrosis throughout the respiratory tract causing pseudomembrane formation which can obstruct the airway Pneumonia may develop and prove fatal 6 Skin exposure mainly causes erythema redness and vesication blistering at first but absorption through the skin causes systemic toxicity In cases where more than 25 of the skin is affected fatal exposure is likely to have occurred 6 Though ingestion is uncommon if mechlorethamine is swallowed it causes severe chemical burns to the gastrointestinal tract and concomitant nausea vomiting diarrhea abdominal pain and hemorrhage 6 Long term effects of acute or chronic chlormethine exposure are caused by damage to the immune system White blood cell counts drop increasing the risk of infection and red blood cell and platelet counts may also drop due to bone marrow damage Chronic eye infections may result from exposure but blindness is temporary Long term effects on the respiratory system include anosmia inability to smell ageusia inability to taste inflammation chronic infections fibrosis and cancer Skin that has been damaged by HN2 can change pigmentation or become scarred and may eventually develop cancer 6 History editThe effect of vesicant blister agents in the form of mustard gas sulfur mustard Bis 2 chloroethyl sulfide on bone marrow and white blood cells had been known since the First World War 16 In 1935 several lines of chemical and biological research yielded results that would be explored after the start of the Second World War The vesicant action of a family of chemicals related to the sulfur mustards but with nitrogen substituting for sulfur was discovered the nitrogen mustards were born 17 The particular nitrogen mustard chlormethine mechlorethamine was first synthesized 18 And the action of sulfur mustard on tumors in laboratory animals was investigated for the first time 19 After the US entry into the Second World War the nitrogen mustards were candidate chemical warfare agents and research on them was initiated by the Office of Scientific Research and Development OSRD The OSRD let contracts to study them to two universities Yale University and the University of Chicago Inspired perhaps by the preliminary research in 1935 independently both groups thought to test whether a medically useful differential toxicity between animals and animal tumors existed 20 The Yale pharmacologists Louis Goodman and Alfred Gilman were the first to conduct a clinical trial on 27 August 1942 using the agent HN3 tris 2 chloroethyl amine on a patient known as J D 21 22 23 The next year the Chicago group led by Leon O Jacobson conducted trials with HN2 chlormethine which was the only agent in this group to see eventual clinical use Wartime secrecy prevented any of this ground breaking work on chemotherapy from being published but papers were released once wartime secrecy ended in 1946 24 Chemistry editChlormethine is combustible and becomes explosive under extreme conditions It can react with metals to form gaseous hydrogen 6 References edit a b c Ledaga Therapeutic Goods Administration TGA 30 June 2021 Archived from the original on 5 September 2021 Retrieved 5 September 2021 a b Ledaga EPAR European Medicines Agency 17 September 2018 Archived from the original on 5 September 2021 Retrieved 5 September 2021 Health product highlights 2021 Annexes of products approved in 2021 Health Canada 3 August 2022 Retrieved 25 March 2024 Rappeneau S Baeza Squiban A Jeulin C Marano F March 2000 Protection from cytotoxic effects induced by the nitrogen mustard mechlorethamine on human bronchial epithelial cells in vitro Toxicol Sci 54 1 212 21 doi 10 1093 toxsci 54 1 212 PMID 10746948 Chapter 3 Principles of Oncologic Pharmacotherapy Cancer Management A Multidisciplinary Approach 2010 Archived from the original on 15 May 2009 Retrieved 8 October 2023 a b c d e f g h i CDC The Emergency Response Safety and Health Database Blister Agent NITROGEN MUSTARD HN 2 NIOSH U S Centers for Disease Control and Prevention CDC Archived from the original on 2019 06 28 Retrieved 2016 04 20 Bunn Jr P A Hoffman S J Norris D Golitz L E Aeling J L 1994 Systemic therapy of cutaneous T cell lymphomas mycosis fungoides and the Sezary syndrome Annals of Internal Medicine 121 8 592 602 doi 10 7326 0003 4819 121 8 199410150 00007 PMID 8085692 S2CID 22909007 Medline 2012 Mechlorethamine Retrieved from https www nlm nih gov medlineplus druginfo meds a682223 html Archived 2016 07 05 at the Wayback Machine Lindahl LM Fenger Gron M Iversen L Topical nitrogen mustard therapy in patients with mycosis fungoides or parapsoriasis J Eur Acad Dermatol Venereol 2013 Feb 27 2 163 8 Galper SL Smith BD Wilson LD Diagnosis and management of mycosis fungoides Oncology Williston Park 2010 May 24 6 491 501 Lessin SR Duvic M Guitart J Pandya AG Strober BE Olsen EA Hull CM Knobler EH Rook AH Kim EJ Naylor MF Adelson DM Kimball AB Wood GS Sundram U Wu H Kim YH Topical chemotherapy in cutaneous T cell lymphoma positive results of a randomized controlled multicenter trial testing the efficacy and safety of a novel mechlorethamine 0 02 gel in mycosis fungoides JAMA Dermatol 2013 Jan 149 1 25 32 McErlane KM Wood RJ Matsui F Lovering EG July 1978 Impurities in Drugs II Meperidine and Its Formulations Journal of Pharmaceutical Sciences 67 7 958 961 doi 10 1002 jps 2600670723 PMID 660515 Recordati Rare Diseases Inc 2013 Mustargen Package Insert Retrieved from https www drugs com pro mustargen html Archived 2018 09 20 at the Wayback Machine Actelion Pharmaceuticals Ltd 2013 Valchlor Package Insert Retrieved from http www accessdata fda gov drugsatfda docs label 2013 202317lbl pdf Archived 2021 03 28 at the Wayback Machine Mustargen Archived 2018 09 20 at the Wayback Machine and Valchlor Archived 2021 03 28 at the Wayback Machine Krumbhaar EB Krumbhaar HD 1919 The blood and bone marrow in yellow cross gas mustard gas poisoning changes produced in the bone marrow of fatal cases J Med Res 40 5 497 508 doi 10 1016 0002 9610 63 90232 0 PMID 13947966 Archived from the original on 2020 02 10 Retrieved 2018 10 14 Ward Kyle 1935 The Chlorinated Ethylamines A New Type of Vesicant J Am Chem Soc 57 5 914 916 doi 10 1021 ja01308a041 V Prelog V Stepan 1935 Nouvele synthese des piperazines N monoalcoylees VIIieme communication sur les bis b halogenoethyl amines Collection of Czechoslovak Chemical Communications 7 93 102 doi 10 1135 cccc19350093 Berenblum I 1935 Experimental inhibition of tumor induction by mustard gas and other compounds Journal of Pathology and Bacteriology 40 3 549 558 doi 10 1002 path 1700400312 Einhorn J 1985 Nitrogen mustard the origin of chemotherapy for cancer Int J Radiat Oncol Biol Phys 11 7 1375 1378 doi 10 1016 0360 3016 85 90254 8 PMID 3891698 Alfred Gilman Frederick S Philips 1946 The Biological Actions and Therapeutic Applications of the B Chloroethyl Amines and Sulfides Science 103 2675 409 436 Bibcode 1946Sci 103 409G doi 10 1126 science 103 2675 409 PMID 17751251 Gilman Alfred 1963 The initial clinical trial of nitrogen mustard Am J Surg 105 5 574 578 doi 10 1016 0002 9610 63 90232 0 PMID 13947966 Fenn John E et al 2011 First Use of Intravenous Chemotherapy Cancer Treatment Rectifying the Record Journal of the American College of Surgeons 212 3 413 417 doi 10 1016 j jamcollsurg 2010 10 018 PMID 21247779 Jacobson L O Spurr C L Barron E Smith T Lushbaugh C Dick G F 1946 Nitrogen Mustard Therapy Studies on the Effect of Methyl Bis Beta Chloroethyl Amine Hydrochloride on Neoplastic Diseases and Allied Disorders of the Hemopoietic System JAMA 132 2675 263 271 doi 10 1001 jama 1946 02870400011003 PMID 20997209 a href Template Cite journal html title Template Cite journal cite journal a CS1 maint multiple names authors list link Portal nbsp Medicine Retrieved from https en wikipedia org w index php title Chlormethine amp oldid 1217080110, wikipedia, wiki, book, books, library,

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