PMC | 1566-15-0 | Alkylating agent

PMC
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WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 464713

CAS#: 1566-15-0 (cyclohexylammonium salt)

Description: Phosphoramide mustard (PMC) is an alkylating agent and active metabolite of cyclophosphamide. It is formed from cyclophosphamide via the ring-opened tautomer of the cytochrome P450 (CYP) isoform-formed intermediate 4-hydroxycyclophosphamide. Phosphoramide mustard induces DNA crosslinking, alkylates guanine in DNA, and increases the production of covalent DNA-protein conjugates in, and is cytotoxic to, HT-1080 human fibrosarcoma cells in a concentration-dependent manner. It is toxic to adult mice and teratogenic to embryos when administered to pregnant dams at a dose of 154 mg/kg on day 11 of gestation.

Chemical Structure

PMC

CAS# 1566-15-0 (cyclohexylammonium salt)

Product data Instruction

Theoretical Analysis

MedKoo Cat#: 464713
Name: PMC
CAS#: 1566-15-0 (cyclohexylammonium salt)
Chemical Formula: C10H24Cl2N3O2P
Exact Mass: 319.10
Molecular Weight: 320.195
Elemental Analysis: C, 37.51; H, 7.56; Cl, 22.14; N, 13.12; O, 9.99; P, 9.67

Price and Availability

Size	Price	Availability
10mg	USD -2	2 Weeks
25mg	USD -2	2 Weeks
50mg	USD -2	2 Weeks
100mg	USD -2	2 Weeks
200mg	USD -2	2 Weeks
500mg	USD -2	2 Weeks
2g	USD -2	2 Weeks
1mg	USD 270	2 Weeks
5mg	USD 580	2 Weeks
Bulk inquiry Welcome, Customer: Please do not inquire quote if your intended use is for a patient since our products are for research use and for chemical synthesis use, not for human use . For in-stock products, we listed price in the web page. You may inquire prices for which sizes were not listed. If no price is listed, this means the product is not in stock at the moment, which may be available via custom synthesis. For cost-effective reason, minimum order of 1g is requested (typically very expensive). The lead time is usually 2-4 months. Quote of less than 1g will not be provided. MedKoo may not offer quote for below reasons: (1) current available synthetic method appears to be extremely expensive which is obviously not affordable to most customers; (2) Key raw material to make the product is temporally not available; (3) DEA controlled substances; (4) the product is under patent protection in customer’s country.

Synonym: PMC; Phosphoramide Mustard cyclohexylammonium salt; NSC 69945; NSC69945; NSC-69945;

IUPAC/Chemical Name: N,N-bis(2-chloroethyl)-phosphorodiamidic acid, compd. with cyclohexanamine

InChi Key: BGTIPRUDEMNRIP-UHFFFAOYSA-N

InChi Code: InChI=1S/C6H13N.C4H11Cl2N2O2P/c7-6-4-2-1-3-5-6;5-1-3-8(4-2-6)11(7,9)10/h6H,1-5,7H2;1-4H2,(H3,7,9,10)

SMILES Code: O=P(N(CCCl)CCCl)(O)N.NC1CCCCC1

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: To be determined

Shelf Life: >2 years if stored properly

Drug Formulation: To be determined

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info:

Product Data:

Product Data

Instruction:

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Biological target:	Phosphoramide mustard (PMC) is an alkylating agent and active metabolite of cyclophosphamide.
In vitro activity:	To investigate whether PM (phosphoramide mustard) induces DNA adduct formation, DNA damage and induction of the DNA repair response, rat spontaneously immortalized granulosa cells (SIGCs) were treated with vehicle control (1% DMSO) or PM (3 or 6μM) for 24 or 48h. Cell viability was reduced (P<0.05) after 48h of exposure to 3 or 6μM PM. The NOR-G-OH DNA adduct was detected after 24h of 6μM PM exposure, while the more cytotoxic G-NOR-G DNA adduct was formed after 48h by exposure to both PM concentrations. Reference: Toxicol Appl Pharmacol. 2015 Feb 1;282(3):252-8. https://pubmed.ncbi.nlm.nih.gov/25497287/
In vivo activity:	In WT mice, PM (phosphoramide mustard) increased 162 and decreased 20 proteins. In Atm+/- mice, 173 and 37 proteins were increased and decreased, respectively, by PM. Exportin-2 (XPO2) was localized to granulosa cells of all follicle stages and was 7.2-fold greater in Atm+/- than WT mice. Cytoplasmic FMR1-interacting protein 1 was 6.8-fold lower in Atm+/- mice and was located in the surface epithelium with apparent translocation to the ovarian medulla post-PM exposure. PM induced γH2AX, but fewer γH2AX-positive foci were identified in Atm+/- ovaries. Similarly, cleaved caspase-3 was lower in the Atm+/- PM-treated, relative to WT mice. Reference: Biol Reprod. 2020 Feb 12;102(1):248-260. https://pubmed.ncbi.nlm.nih.gov/31435664/

Solubility Data

	Solvent	Max Conc. mg/mL	Max Conc. mM
Solubility
	Water	100.0	312.31

Preparing Stock Solutions

The following data is based on the product molecular weight 320.19 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:	1. Madden JA, Thomas PQ, Keating AF. Phosphoramide mustard induces autophagy markers and mTOR inhibition prevents follicle loss due to phosphoramide mustard exposure. Reprod Toxicol. 2017 Jan;67:65-78. doi: 10.1016/j.reprotox.2016.11.014. Epub 2016 Nov 22. PMID: 27888070. 2. Ganesan S, Keating AF. Phosphoramide mustard exposure induces DNA adduct formation and the DNA damage repair response in rat ovarian granulosa cells. Toxicol Appl Pharmacol. 2015 Feb 1;282(3):252-8. doi: 10.1016/j.taap.2014.11.017. Epub 2014 Dec 9. PMID: 25497287; PMCID: PMC5044804. 3. Clark KL, Keating AF. Ataxia-telangiectasia mutated coordinates the ovarian DNA repair and atresia-initiating response to phosphoramide mustard. Biol Reprod. 2020 Feb 12;102(1):248-260. doi: 10.1093/biolre/ioz160. PMID: 31435664. 4. Ganesan S, Nteeba J, Madden JA, Keating AF. Obesity alters phosphoramide mustard-induced ovarian DNA repair in mice. Biol Reprod. 2017 Feb 1;96(2):491-501. doi: 10.1095/biolreprod.116.143800. PMID: 28203708; PMCID: PMC6366544.
In vitro protocol:	1. Madden JA, Thomas PQ, Keating AF. Phosphoramide mustard induces autophagy markers and mTOR inhibition prevents follicle loss due to phosphoramide mustard exposure. Reprod Toxicol. 2017 Jan;67:65-78. doi: 10.1016/j.reprotox.2016.11.014. Epub 2016 Nov 22. PMID: 27888070. 2. Ganesan S, Keating AF. Phosphoramide mustard exposure induces DNA adduct formation and the DNA damage repair response in rat ovarian granulosa cells. Toxicol Appl Pharmacol. 2015 Feb 1;282(3):252-8. doi: 10.1016/j.taap.2014.11.017. Epub 2014 Dec 9. PMID: 25497287; PMCID: PMC5044804.
In vivo protocol:	1. Clark KL, Keating AF. Ataxia-telangiectasia mutated coordinates the ovarian DNA repair and atresia-initiating response to phosphoramide mustard. Biol Reprod. 2020 Feb 12;102(1):248-260. doi: 10.1093/biolre/ioz160. PMID: 31435664. 2. Ganesan S, Nteeba J, Madden JA, Keating AF. Obesity alters phosphoramide mustard-induced ovarian DNA repair in mice. Biol Reprod. 2017 Feb 1;96(2):491-501. doi: 10.1095/biolreprod.116.143800. PMID: 28203708; PMCID: PMC6366544.

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1: Ponticelli C, Escoli R, Moroni G. Does cyclophosphamide still play a role in glomerular diseases? Autoimmun Rev. 2018 Oct;17(10):1022-1027. doi: 10.1016/j.autrev.2018.04.007. Epub 2018 Aug 11. PMID: 30107267.

2: Iqubal A, Iqubal MK, Sharma S, Ansari MA, Najmi AK, Ali SM, Ali J, Haque SE. Molecular mechanism involved in cyclophosphamide-induced cardiotoxicity: Old drug with a new vision. Life Sci. 2019 Feb 1;218:112-131. doi: 10.1016/j.lfs.2018.12.018. Epub 2018 Dec 12. PMID: 30552952.

3: Ganesan S, Nteeba J, Madden JA, Keating AF. Obesity alters phosphoramide mustard-induced ovarian DNA repair in mice. Biol Reprod. 2017 Feb 1;96(2):491-501. doi: 10.1095/biolreprod.116.143800. PMID: 28203708; PMCID: PMC6366544.

4: Plowchalk DR, Mattison DR. Phosphoramide mustard is responsible for the ovarian toxicity of cyclophosphamide. Toxicol Appl Pharmacol. 1991 Mar 1;107(3):472-81. doi: 10.1016/0041-008x(91)90310-b. PMID: 2000634.

5: Li D, Dai L, Zhao X, Zhi S, Shen H, Yang Z. Novel Sophoridine Derivatives Bearing Phosphoramide Mustard Moiety Exhibit Potent Antitumor Activities In Vitro and In Vivo. Molecules. 2018 Aug 6;23(8):1960. doi: 10.3390/molecules23081960. PMID: 30082625; PMCID: PMC6222802.

6: Clark KL, Keating AF. Ataxia-telangiectasia mutated coordinates the ovarian DNA repair and atresia-initiating response to phosphoramide mustard. Biol Reprod. 2020 Feb 12;102(1):248-260. doi: 10.1093/biolre/ioz160. PMID: 31435664.

7: Watson E, Dea P, Chan KK. Kinetics of phosphoramide mustard hydrolysis in aqueous solution. J Pharm Sci. 1985 Dec;74(12):1283-92. doi: 10.1002/jps.2600741208. PMID: 4087195.

8: Juma FD, Rogers HJ, Trounce JR. The pharmacokinetics of cyclophosphamide, phosphoramide mustard and nor-nitrogen mustard studied by gas chromatography in patients receiving cyclophosphamide therapy. Br J Clin Pharmacol. 1980 Oct;10(4):327-35. doi: 10.1111/j.1365-2125.1980.tb01768.x. PMID: 7448105; PMCID: PMC1430090.

9: Madden JA, Thomas PQ, Keating AF. Phosphoramide mustard induces autophagy markers and mTOR inhibition prevents follicle loss due to phosphoramide mustard exposure. Reprod Toxicol. 2017 Jan;67:65-78. doi: 10.1016/j.reprotox.2016.11.014. Epub 2016 Nov 22. PMID: 27888070.

10: Zhang W, Fan W, Zhou Z, Garrison J. Synthesis and Evaluation of Radiolabeled Phosphoramide Mustard with Selectivity for Hypoxic Cancer Cells. ACS Med Chem Lett. 2017 Oct 23;8(12):1269-1274. doi: 10.1021/acsmedchemlett.7b00355. PMID: 29259746; PMCID: PMC5733275.

11: Hales BF. Effects of phosphoramide mustard and acrolein, cytotoxic metabolites of cyclophosphamide, on mouse limb development in vitro. Teratology. 1989 Jul;40(1):11-20. doi: 10.1002/tera.1420400103. PMID: 2763206.

12: Groehler A 4th, Villalta PW, Campbell C, Tretyakova N. Covalent DNA-Protein Cross-Linking by Phosphoramide Mustard and Nornitrogen Mustard in Human Cells. Chem Res Toxicol. 2016 Feb 15;29(2):190-202. doi: 10.1021/acs.chemrestox.5b00430. Epub 2016 Jan 20. PMID: 26692166; PMCID: PMC4755881.

13: Madden JA, Hoyer PB, Devine PJ, Keating AF. Involvement of a volatile metabolite during phosphoramide mustard-induced ovotoxicity. Toxicol Appl Pharmacol. 2014 May 15;277(1):1-7. doi: 10.1016/j.taap.2014.03.006. Epub 2014 Mar 15. PMID: 24642057; PMCID: PMC4077164.

14: Ganesan S, Keating AF. Phosphoramide mustard exposure induces DNA adduct formation and the DNA damage repair response in rat ovarian granulosa cells. Toxicol Appl Pharmacol. 2015 Feb 1;282(3):252-8. doi: 10.1016/j.taap.2014.11.017. Epub 2014 Dec 9. PMID: 25497287; PMCID: PMC5044804.

15: Colvin M, Brundrett RB, Kan MN, Jardine I, Fenselau C. Alkylating properties of phosphoramide mustard. Cancer Res. 1976 Mar;36(3):1121-6. PMID: 1253171.

16: Chen B, Cyr DG, Hales BF. Role of apoptosis in mediating phosphoramide mustard-induced rat embryo malformations in vitro. Teratology. 1994 Jul;50(1):1-12. doi: 10.1002/tera.1420500102. PMID: 7974249.

17: Wu X, Hu L. Design and synthesis of peptide conjugates of phosphoramide mustard as prodrugs activated by prostate-specific antigen. Bioorg Med Chem. 2016 Jun 15;24(12):2697-706. doi: 10.1016/j.bmc.2016.04.035. Epub 2016 Apr 19. PMID: 27156193.

18: Madden JA, Keating AF. Ovarian xenobiotic biotransformation enzymes are altered during phosphoramide mustard-induced ovotoxicity. Toxicol Sci. 2014 Oct;141(2):441-52. doi: 10.1093/toxsci/kfu146. Epub 2014 Jul 28. Erratum in: Toxicol Sci. 2015 May;145(1):209-10. PMID: 25070981; PMCID: PMC4271048.

19: Low JE, Borch RF, Sladek NE. Conversion of 4-hydroperoxycyclophosphamide and 4-hydroxycyclophosphamide to phosphoramide mustard and acrolein mediated by bifunctional catalysis. Cancer Res. 1982 Mar;42(3):830-7. PMID: 7059981.

20: Dong Q, Barsky D, Colvin ME, Melius CF, Ludeman SM, Moravek JF, Colvin OM, Bigner DD, Modrich P, Friedman HS. A structural basis for a phosphoramide mustard-induced DNA interstrand cross-link at 5'-d(GAC). Proc Natl Acad Sci U S A. 1995 Dec 19;92(26):12170-4. doi: 10.1073/pnas.92.26.12170. PMID: 8618865; PMCID: PMC40318.

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