PHY34

PHY34 is an inhibitor that inhibits ATP6V0A2 and CAS thereby inhibiting autophagy, and has a nanomolar effect. PHY34 inhibits cancer cell growth by inducing apoptosis and inhibits tumor growth in xenograft models. PHY34 can be used for research on high grade serous ovarian cancer^[1][2]. IC50 & Target:ATP6V0A2, cellular apoptosis susceptibility (CAS)^[2] In Vitro:PHY34 (0.001 nM-50 μM, 72 h) inhibits various cancer cells growth with nanomolar potency through activation of apoptosis based on enhanced cPARP levels and has the highest potency in HGSOC cell lines^[1].
PHY34 (100 nM, 1 μM; 24 h) blocks the final breakdown of the autolysosomes in OVCAR8 at 100 nM, and in OVCAR3 at 1 μM, respectively^[1].
PHY34 (10 nM, 24 h) inhibits the late-stage autophagy that precedes apoptosis induction in OVCAR8^[1].
PHY34 (100 nM, 48 h) inhibits the late-stage autophagy that precedes apoptosis induction in OVCAR3^[1].
PHY34 (0.01 nM-2 μM, 72 h) induces cell death in the presence of wild-type V0A2, but not V823I mutants in H4 cell^[2].
PHY34 (10, 100 nM; 48 h, 72 h) changes subcellular localization of nuclear multiple proteins^[2].
PHY34 (20 μM, 1 h) binds specificity with ATP6V0A2 subunit^[2].
In Vivo:PHY34 (0.75 mg/kg, i.p., 3 times a week for 3 weeks) inhibits tumor growth and reduces Ki67 expression in tumor tissue in a female nude mouse tumor bearing model constructed by OVCAR8^[1].

PHY34 Pharmacokinetics^[1]

药代动力学分析^[1]

Parameter	Units	IV	IP	PO
Dose	mg/kg	0.6	1.8	75
Dose	nmol	1029.9	3089.8	128742.1
T1/2	hr	6.2	8.4	12.3
Tmax	hr	0.08	0.25	0.25
Cmax	nmol/L	288.8	519.5	323.6
AUClast	hr*nmol/L	198.8	360.5	599.9
AUCinf	hr*nmol/L	215.8	366.5	663.3
Vz	L/kg	42.7	101.6	3430.3
CI	L/hr/kg	4.8	8.4	194.1
MRT	hr	6.1	1.9	7.8
F*	%	-	56.6	2.5