PF-06380101

Names

[ Name ]:
PF-06380101

[Synonym ]:
2-Methyl-L-Alanyl-N-[(3r,4s,5s)-3-Methoxy-1-{(2s)-2-[(1r,2r)-1-Methoxy-2-Methyl-3-Oxo-3-{[(1s)-2-Phenyl-1-(1,3-Thiazol-2-Yl)ethyl]amino}propyl]pyrrolidin-1-Yl}-5-Methyl-1-Oxoheptan-4-Yl]-N-Methyl-L-Valinamide
2-Methyl-L-alanyl-N-[(3R,4S,5S)-3-methoxy-1-{(2S)-2-[(1R,2R)-1-methoxy-2-methyl-3-oxo-3-{[(1S)-2-phenyl-1-(1,3-thiazol-2-yl)ethyl]amino}propyl]-1-pyrrolidinyl}-5-methyl-1-oxo-4-heptanyl]-N-methyl-L-valinamide
L-Valinamide, 2-methyl-L-alanyl-N-[(1S,2R)-2-methoxy-4-[(2S)-2-[(1R,2R)-1-methoxy-2-methyl-3-oxo-3-[[(1S)-2-phenyl-1-(2-thiazolyl)ethyl]amino]propyl]-1-pyrrolidinyl]-1-[(1S)-1-methylpropyl]-4-oxobutyl]-N-methyl-
Q8020AX34E

Biological Activity

[Description]:

PF-06380101 is a novel cytotoxic Dolastatin 10 analogue; with excellent potencies in tumor cell proliferation assays and differential ADME properties when compared to other synthetic auristatin analogues that are used in the preparation of ADCs.IC50 value: ~0.2 nM(GI50 in BT474, MDA-MB-361-DYT2 and N87 cell line) [1]Target: ADCs cytotoxin; tubulin inhibitorAfter an IV dose of 20a at 20 μg/kg to Wistar Han rats, PF-06380101 exhibited a mean systemic clearance (Cl) of 70 mL/min/kg and a volume of distribution (Vss) of 14.70 L/kg, resulting in a terminal elimination half-life (t1/2) of approximately 6 h. PF-06380101 preferentially distributes into human plasma relative to whole blood and that PF-06380101 is a P-glycoprotein (P-gp) substrate. PF-06380101 is anticipated to be of low risk to perpetrate pharmacokinetic drug interactions with compounds for which CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and/or CYP3A4/5-mediated metabolism constitutes the primary mechanism of clearance. The utility of the new auristatin analogues as ADC payloads including the development of the lead analogue 20a (PF-06380101) will be reported in due course.

[Related Catalog]:

Signaling Pathways >> Antibody-drug Conjugate >> ADC Cytotoxin

Signaling Pathways >> Cell Cycle/DNA Damage >> Microtubule/Tubulin

Signaling Pathways >> Cytoskeleton >> Microtubule/Tubulin

Research Areas >> Cancer

[References]

[1]. Maderna A, et al. Discovery of cytotoxic dolastatin 10 analogues with N-terminal modifications. J Med Chem. 2014 Dec 26;57(24):10527-43.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.1±0.1 g/cm3

[ Boiling Point ]:
903.1±65.0 °C at 760 mmHg

[ Molecular Formula ]:
C₃₉H₆₂N₆O₆S

[ Molecular Weight ]:
743.011

[ Flash Point ]:
500.0±34.3 °C

[ Exact Mass ]:
742.445129

[ LogP ]:
5.05

[ Vapour Pressure ]:
0.0±0.3 mmHg at 25°C

[ Index of Refraction ]:
1.546

[ Storage condition ]:
2-8℃

Related Compounds

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