DM4 hydrate
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    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 464823

CAS#: unknown

Description: DM4 is a thiol-containing derivative of the tubulin polymerization inhibitor maytansine. It is cytotoxic to SK-BR-3 cells (IC50 = 3.3 nM). DM4, conjugated to a humanized CD205-targeting monoclonal antibody, is selectively cytotoxic to a variety of CD205-expressing human cancer cells (EC50s = 0.1-1.32 nM) over non-CD205-expressing cells (EC50s = 14.2-22.66 nM) and reduces tumor growth in various mouse xenograft and patient-derived (PDX) cancer models.

Chemical Structure

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DM4 hydrate
CAS# unknown
Instruction

Theoretical Analysis

MedKoo Cat#: 464823
Name: DM4 hydrate
CAS#: unknown
Chemical Formula: C38H56ClN3O11S
Exact Mass: 797.33
Molecular Weight: 798.386
Elemental Analysis: C, 57.17; H, 7.07; Cl, 4.44; N, 5.26; O, 22.04; S, 4.02

Price and Availability

Size Price Availability Quantity
5mg USD 300 2 Weeks
10mg USD 550 2 Weeks
25mg USD 950 2 Weeks
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Synonym: DM4 hydrate; DM4-hydrate; Maytansinoid DM 4; Maytansinoid DM4; Maytansinoid DM-4;

IUPAC/Chemical Name: (14S,16S,32S,33S,2R,4S,10E,12E,14R)-86-chloro-14-hydroxy-85,14-dimethoxy-33,2,7,10-tetramethyl-12,6-dioxo-7-aza-1(6,4)-oxazinana-3(2,3)-oxirana-8(1,3)-benzenacyclotetradecaphane-10,12-dien-4-yl N-(4-mercapto-4-methylpentanoyl)-N-methyl-L-alaninate hydrate

InChi Key: UDQFYEYHHMGCNT-YFGFGYKHSA-N

InChi Code: InChI=1S/C38H54ClN3O10S.H2O/c1-21-12-11-13-28(49-10)38(47)20-27(50-35(46)40-38)22(2)33-37(6,52-33)29(51-34(45)23(3)41(7)30(43)14-15-36(4,5)53)19-31(44)42(8)25-17-24(16-21)18-26(48-9)32(25)39;/h11-13,17-18,22-23,27-29,33,47,53H,14-16,19-20H2,1-10H3,(H,40,46);1H2/b13-11+,21-12+;/t22-,23+,27+,28-,29+,33+,37+,38+;/m1./s1

SMILES Code: C[C@@]12[C@@]([H])(O2)[C@H](C)[C@@]3(C[C@](NC(O3)=O)(O)[C@H](OC)/C=C/C=C(C)/CC4=CC(N(C)C(C[C@@H]1OC([C@@H](N(C(CCC(S)(C)C)=O)C)C)=O)=O)=C(C(OC)=C4)Cl)[H].O

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:

Biological target:
In vitro activity:
In vivo activity:

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMF 30.0 37.58
DMSO 30.0 37.58
Ethanol 20.0 25.05

Preparing Stock Solutions

The following data is based on the product molecular weight 798.39 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.

Recalculate based on batch purity %
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:
In vitro protocol:
In vivo protocol:

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1: Li W, Huang M, Li Y, Xia A, Tan L, Zhang Z, Wang Y, Yang J. C3 ester side chain plays a pivotal role in the antitumor activity of Maytansinoids. Biochem Biophys Res Commun. 2021 Jun 15;566:197-203. doi: 10.1016/j.bbrc.2021.05.071. Epub ahead of print. PMID: 34144258.

2: Moore KN, Oza AM, Colombo N, Oaknin A, Scambia G, Lorusso D, Konecny GE, Banerjee S, Murphy CG, Tanyi JL, Hirte H, Konner JA, Lim PC, Prasad-Hayes M, Monk BJ, Pautier P, Wang J, Berkenblit A, Vergote I, Birrer MJ. Phase III, randomized trial of mirvetuximab soravtansine versus chemotherapy in patients with platinum-resistant ovarian cancer: primary analysis of FORWARD I. Ann Oncol. 2021 Jun;32(6):757-765. doi: 10.1016/j.annonc.2021.02.017. Epub 2021 Mar 2. PMID: 33667670.

3: Porter J, Ding Y, Hale SJM, Perrins RD, Robinson A, Mazanetz MP, Wu Y, Ma Y, Conlon K, Coulter T. A highly potent maytansinoid analogue and its use as a cytotoxic therapeutic agent in gold nanoparticles for the treatment of hepatocellular carcinoma. Bioorg Med Chem Lett. 2020 Dec 15;30(24):127634. doi: 10.1016/j.bmcl.2020.127634. Epub 2020 Oct 22. PMID: 33148516.

4: Nittoli T, Delfino F, Kelly M, Carosso S, Markotan T, Kunz A, Chen Z, Mao S, Shan J, Navarro E, Zhao F, Makonnen S, Hickey C, Spink J, Olson W, Kirshner JR, Thurston G, Papadopoulos N. Antibody drug conjugates of cleavable amino-benzoyl- maytansinoids. Bioorg Med Chem. 2020 Dec 1;28(23):115785. doi: 10.1016/j.bmc.2020.115785. Epub 2020 Oct 11. PMID: 33099182.

5: Hassan R, Blumenschein GR Jr, Moore KN, Santin AD, Kindler HL, Nemunaitis JJ, Seward SM, Thomas A, Kim SK, Rajagopalan P, Walter AO, Laurent D, Childs BH, Sarapa N, Elbi C, Bendell JC. First-in-Human, Multicenter, Phase I Dose- Escalation and Expansion Study of Anti-Mesothelin Antibody-Drug Conjugate Anetumab Ravtansine in Advanced or Metastatic Solid Tumors. J Clin Oncol. 2020 Jun 1;38(16):1824-1835. doi: 10.1200/JCO.19.02085. Epub 2020 Mar 26. PMID: 32213105; PMCID: PMC7255978.

6: O'Malley DM, Matulonis UA, Birrer MJ, Castro CM, Gilbert L, Vergote I, Martin LP, Mantia-Smaldone GM, Martin AG, Bratos R, Penson RT, Malek K, Moore KN. Phase Ib study of mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), in combination with bevacizumab in patients with platinum-resistant ovarian cancer. Gynecol Oncol. 2020 May;157(2):379-385. doi: 10.1016/j.ygyno.2020.01.037. Epub 2020 Feb 18. PMID: 32081463.

7: Gao S, Zhang W, Wang R, Hopkins SP, Spagnoli JC, Racin M, Bai L, Li L, Jiang W, Yang X, Lee C, Nagata K, Howerth EW, Handa H, Xie J, Ma Q, Kumar A. Nanoparticles Encapsulating Nitrosylated Maytansine To Enhance Radiation Therapy. ACS Nano. 2020 Feb 25;14(2):1468-1481. doi: 10.1021/acsnano.9b05976. Epub 2020 Jan 21. PMID: 31939662.

8: Harel ET, Drake PM, Barfield RM, Lui I, Farr-Jones S, Van't Veer L, Gartner ZJ, Green EM, Lourenço AL, Cheng Y, Hann BC, Rabuka D, Craik CS. Antibody-Drug Conjugates Targeting the Urokinase Receptor (uPAR) as a Possible Treatment of Aggressive Breast Cancer. Antibodies (Basel). 2019 Nov 5;8(4):54. doi: 10.3390/antib8040054. PMID: 31694242; PMCID: PMC6963874.

9: Heo GS, Detering L, Luehmann HP, Primeau T, Lee YS, Laforest R, Li S, Stec J, Lim KH, Lockhart AC, Liu Y. Folate Receptor α-Targeted 89Zr-M9346A Immuno-PET for Image-Guided Intervention with Mirvetuximab Soravtansine in Triple-Negative Breast Cancer. Mol Pharm. 2019 Sep 3;16(9):3996-4006. doi: 10.1021/acs.molpharmaceut.9b00653. Epub 2019 Aug 16. PMID: 31369274.

10: Zhang D, Dragovich PS, Yu SF, Ma Y, Pillow TH, Sadowsky JD, Su D, Wang W, Polson A, Khojasteh SC, Hop CECA. Exposure-Efficacy Analysis of Antibody-Drug Conjugates Delivering an Excessive Level of Payload to Tissues. Drug Metab Dispos. 2019 Oct;47(10):1146-1155. doi: 10.1124/dmd.119.087023. Epub 2019 Jul 29. PMID: 31358513.

11: Yoder NC, Bai C, Tavares D, Widdison WC, Whiteman KR, Wilhelm A, Wilhelm SD, McShea MA, Maloney EK, Ab O, Wang L, Jin S, Erickson HK, Keating TA, Lambert JM. A Case Study Comparing Heterogeneous Lysine- and Site-Specific Cysteine- Conjugated Maytansinoid Antibody-Drug Conjugates (ADCs) Illustrates the Benefits of Lysine Conjugation. Mol Pharm. 2019 Sep 3;16(9):3926-3937. doi: 10.1021/acs.molpharmaceut.9b00529. Epub 2019 Jul 31. PMID: 31287952.

12: Merlino G, Fiascarelli A, Bigioni M, Bressan A, Carrisi C, Bellarosa D, Salerno M, Bugianesi R, Manno R, Bernadó Morales C, Arribas J, Dusek RL, Ackroyd JE, Pham PH, Awdew R, Aud D, Trang M, Lynch CM, Terrett J, Wilson KE, Rohlff C, Manzini S, Pellacani A, Binaschi M. MEN1309/OBT076, a First-In-Class Antibody- Drug Conjugate Targeting CD205 in Solid Tumors. Mol Cancer Ther. 2019 Sep;18(9):1533-1543. doi: 10.1158/1535-7163.MCT-18-0624. Epub 2019 Jun 21. PMID: 31227646.

13: Huhe M, Lou J, Zhu Y, Zhao Y, Shi Y, Wang B, Sun X, Zhang X, Zhang Y, Chen ZN. A novel antibody-drug conjugate, HcHAb18-DM1, has potent anti-tumor activity against human non-small cell lung cancer. Biochem Biophys Res Commun. 2019 Jun 11;513(4):1083-1091. doi: 10.1016/j.bbrc.2019.04.046. Epub 2019 Apr 19. PMID: 31010682.

14: Sun Y, Liang Y, Dai W, He B, Zhang H, Wang X, Wang J, Huang S, Zhang Q. Peptide-Drug Conjugate-Based Nanocombination Actualizes Breast Cancer Treatment by Maytansinoid and Photothermia with the Assistance of Fluorescent and Photoacoustic Images. Nano Lett. 2019 May 8;19(5):3229-3237. doi: 10.1021/acs.nanolett.9b00770. Epub 2019 Apr 11. PMID: 30957499.

15: White BH, Whalen K, Kriksciukaite K, Alargova R, Au Yeung T, Bazinet P, Brockman A, DuPont M, Oller H, Lemelin CA, Lim Soo P, Moreau B, Perino S, Quinn JM, Sharma G, Shinde R, Sweryda-Krawiec B, Wooster R, Bilodeau MT. Discovery of an SSTR2-Targeting Maytansinoid Conjugate (PEN-221) with Potent Activity in Vitro and in Vivo. J Med Chem. 2019 Mar 14;62(5):2708-2719. doi: 10.1021/acs.jmedchem.8b02036. Epub 2019 Feb 28. PMID: 30735385.

16: Zhang X, Zhang C, Yang X, Hou X, Zhao W, Benson D, Yu J, Dong Y. Design, synthesis and evaluation of anti-CD38 antibody drug conjugate based on Daratumumab and maytansinoid. Bioorg Med Chem. 2019 Feb 1;27(3):479-482. doi: 10.1016/j.bmc.2018.12.024. Epub 2018 Dec 16. PMID: 30594452; PMCID: PMC6339845.

17: Xie K, Song S, Zhou L, Wan J, Qiao Y, Wang M, Xie H, Zhou L, Zheng S, Wang H. Revival of a potent therapeutic maytansinoid agent using a strategy that combines covalent drug conjugation with sequential nanoparticle assembly. Int J Pharm. 2019 Feb 10;556:159-171. doi: 10.1016/j.ijpharm.2018.12.017. Epub 2018 Dec 13. PMID: 30553007.

18: Kinneer K, Meekin J, Tiberghien AC, Tai YT, Phipps S, Kiefer CM, Rebelatto MC, Dimasi N, Moriarty A, Papadopoulos KP, Sridhar S, Gregson SJ, Wick MJ, Masterson L, Anderson KC, Herbst R, Howard PW, Tice DA. SLC46A3 as a Potential Predictive Biomarker for Antibody-Drug Conjugates Bearing Noncleavable Linked Maytansinoid and Pyrrolobenzodiazepine Warheads. Clin Cancer Res. 2018 Dec 15;24(24):6570-6582. doi: 10.1158/1078-0432.CCR-18-1300. Epub 2018 Aug 21. PMID: 30131388.

19: Jiang Z, Yang Z, Li F, Li Z, Fishkin N, Burgess K. Targeted Maytansinoid Conjugate Improves Therapeutic Index for Metastatic Breast Cancer Cells. Bioconjug Chem. 2018 Sep 19;29(9):2920-2926. doi: 10.1021/acs.bioconjchem.8b00340. Epub 2018 Aug 13. PMID: 30102524.

20: Nittoli T, Kelly MP, Delfino F, Rudge J, Kunz A, Markotan T, Spink J, Chen Z, Shan J, Navarro E, Tait M, Provoncha K, Giurleo J, Zhao F, Jiang X, Hylton D, Makonnen S, Hickey C, Kirshner JR, Thurston G, Papadopoulos N. Antibody drug conjugates of cleavable amino-alkyl and aryl maytansinoids. Bioorg Med Chem. 2018 May 15;26(9):2271-2279. doi: 10.1016/j.bmc.2018.02.025. Epub 2018 Feb 21. PMID: 29605304.