D8-MMAF hydrochloride

D8-MMAF hydrochloride is a deuterated form of MMAF hydrochloride, which is a microtubule disrupting agent.

Product information

Molecular Weight: 776.47

Formula: C39H66ClN5O8

Chemical Name: (2S)-2-[(2R)-2-[(R)-methoxy[(2S)-1-[(3R, 4S, 5S)-3-methoxy-5-methyl-4-[(2S)-3-(H)methyl-N-methyl-2-[(2S)-3-methyl-2-(methylamino)butanamido](2, 3, 4, 4, 4-H)butanamido]heptanoyl]pyrrolidin-2-yl]methyl]propanamido]-3-phenylpropanoic acid hydrochloride

Smiles: Cl.[2H]C([C@]([2H])(NC(=O)[C@@H](NC)C(C)C)C(=O)N(C)[C@H]([C@@H](CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=O)N[C@@H](CC1C=CC=CC=1)C(O)=O)OC)[C@@H](C)CC)(C([2H])([2H])[2H])C([2H])([2H])[2H]

InChiKey: BUPKFQQDMNUXOY-HKTWAXPZSA-N

InChi: InChI=1S/C39H65N5O8.ClH/c1-12-25(6)34(43(9)38(48)33(24(4)5)42-37(47)32(40-8)23(2)3)30(51-10)22-31(45)44-20-16-19-29(44)35(52-11)26(7)36(46)41-28(39(49)50)21-27-17-14-13-15-18-27;/h13-15,17-18,23-26,28-30,32-35,40H,12,16,19-22H2,1-11H3,(H,41,46)(H,42,47)(H,49,50);1H/t25-,26+,28-,29-,30+,32-,33-,34-,35+;/m0./s1/i4D3,5D3,24D,33D;

Technical Data

Appearance: Solid Power

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

Solubility: Soluble in DMSO

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥360 days if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

MMAF shows in vitro cytotoxicity against a panel of cell lines. The IC50 values for Karpas 299, H3396, 786-O and Caki-1 are 119, 105, 257, and 200 nM, respectively. Targeted MMAF is much more potent than the free drug, and that cAC10 conjugates of MMAF display pronounced activities. On a molar basis, the cAC10-L1-MMAF4 is an average of over 2200-fold more potent than free MMAF and is active on all the CD30-positive cell lines tested.

In Vivo:

The maximum tolerated dose in mice of MMAF (>16 mg/kg) is much higher than MMAE (1 mg/kg). cAC10-L1-MMAF4 has an MTD of 50 mg/kg in mice and 15 mg/kg in rats. The corresponding cAC10-L4-MMAF4 ADC was much less toxic, having MTDs in mice and rats of >150 mg/ kg and 90 mg/kg in rats, respectively.

References:

1. Doronina SO, et al. Enhanced activity of monomethylauristatin F through monoclonal antibody delivery: effects of linker technology on efficacy and toxicity. Bioconjug Chem. 2006 Jan-Feb;17(1):114-24.

Products are for research use only. Not for human use.