| Identification | Back Directory | [Name]
N-[6-[3-[[(2R)-2-Amino-2-carboxyethyl]thio]-2,5-dioxo-1-pyrrolidinyl]-1-oxohexyl]-N-methyl-L-valyl-L-valyl-(3R,4S,5S)-3-methoxy-5-methyl-4-(methylamino)heptanoyl-(αR,βR,2S)-β-methoxy-α-methyl-2-pyrrolidinepropanoyl-L-phenylalanine | [CAS]
1160590-05-5 | [Synonyms]
Cys-McMMAF
N-[6-[3-[[(2R)-2-Amino-2-carboxyethyl]thio]-2,5-dioxo-1-pyrrolidinyl]-1-oxohexyl]-N-methyl-L-valyl-L-valyl-(3R,4S,5S)-3-methoxy-5-methyl-4-(methylamino)heptanoyl-(αR,βR,2S)-β-methoxy-α-methyl-2-pyrrolidinepropanoyl-L-phenylalanine | [Molecular Formula]
C52H83N7O13S | [MOL File]
1160590-05-5.mol | [Molecular Weight]
1046.32 |
| Chemical Properties | Back Directory | [Boiling point ]
1172.4±65.0 °C(Predicted) | [density ]
1.25±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted) | [form ]
Solid | [pka]
2.02±0.10(Predicted) | [color ]
White to off-white |
| Hazard Information | Back Directory | [Uses]
Cys-McMMAF is the released payload of AlMcMMAF, an anti-5T4 humanized A1 antibody conjugated to the microtubule disrupting MMAF (HY-15579) via a maleimidocaproyl linker. Cys-McMMAF has antitumor efficacy in two tumor mouse models (H1975 and MDA-MB-361-DYT2 models)[1]. | [in vivo]
Cys-McMMAF (0.3 mg/kg, 3 mg/kg; i.v.; single dose) has a poor stability with short decline time in cynomolgus monkeys[1].
Pharmacokinetic Analysis in Nude (nu/nu) Mice[1]
| Model/IV | Dose (mg/kg) | Cmax (ng/mL) | Tmax (hr) | AUC0-336 (ng·h/mL) | t1/2 (day) | | Non-Tumor | 1 | 0.192 | 8 | 14.6 | 2.1 | | Tumor | 1 | 0.146 | 8 | 28.2 | 6.0 | | Non-Tumor | 10 | 0.951 | 8 | 58.5 | 3.0 | | Tumor | 10 | 0.945 | 8 | 81.9/td>
| 2.9 |
| [References]
[1] Leal M, et al. Preclinical Development of an anti-5T4 Antibody-Drug Conjugate: Pharmacokinetics in Mice, Rats, and NHP and Tumor/Tissue Distribution in Mice. Bioconjug Chem. 2015 Nov 18;26(11):2223-32. DOI:10.1021/acs.bioconjchem.5b00205 |
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