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3032451-66-1

3032451-66-1 Structure

3032451-66-1 Structure
IdentificationBack Directory
[Name]

4-(3-(3-(5-bromofuran-2-yl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine-7-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one
[CAS]

3032451-66-1
[Synonyms]

4-(3-(3-(5-bromofuran-2-yl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine-7-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one
[Molecular Formula]

C25H18BrFN6O3
[MOL File]

3032451-66-1.mol
[Molecular Weight]

549.35
Chemical PropertiesBack Directory
[density ]

1.715±0.14 g/cm3(Temp: 25 °C; Press: 760 Torr)(predicted)
[solubility ]

DMSO: Soluble
[form ]

Solid
[pka]

12.059±0.40(predicted)
[color ]

White to off-white
Hazard InformationBack Directory
[Uses]

YCH1899 is an orally active PARP inhibitor, with an IC50< 0.001 nM for PARP1/2. YCH1899 exhibits distinct antiproliferation activity against Olaparib (HY-10162)-resistant and Talazoparib (HY-16106)-resistant Capan-1 cells (Capan-1/OP and Capan-1/TP cells) , with IC50 values of 0.89 and 1.13 nM, respectively. YCH1899 has acceptable pharmacokinetic properties in rats[1].
[in vivo]

YCH1899 (5 mg/kg, intravenous injection ) has a moderate clearance rate in rats[1].
YCH1899 overcomes acquired Talazoparib resistance and has a significant regression of tumor volume in MDA-MB-436/OP (6.25, 12.5, and 25 mg/kg, orally, once a day for 27 days) and Capan-1/R-in vivo xenografts (12.5 and 25 mg/kg, orally, once a day for 21 days ) [1].

Animal Model:MDA-MB-436/OP xenografts and Capan-1/R-in vivo xenografts mice[1]
Dosage:12.5 and 25 mg/kg
Administration:Oral administration
Result:Inhibited MDA-MB-436/OP xenografts tumor growth with T/C of 36.74% and 15.29% at 12.5 and 25 mg/kg
Inhibited Capan-1/R xenografts tumor growth with T/C of 48.92% and 13.87% at 12.5 and 25 mg/kg.
Animal Model:rats[1]
Dosage:5 mg/kg
Administration:Intravenous injection
Result:Had a moderate clearance rate (24.5 mL/min/kg) and half-life (3.25 h).
[IC 50]

PARP-1: <0.001 nM (IC50); PARP-2: <0.001 nM (IC50); PARP3: 1.1 nM (IC50); PARP4: 1.0 nM (IC50); TNKS1: 3.8 nM (EC50); TNKS2: 12.4 nM (IC50); PARA6: 9.5 nM (IC50); PARP-7: 7.3 nM (IC50); ARTD10/PARP10: 10.8 nM (IC50); PARA11: 2.166 μM (IC50); human PARP12: 14.1 nM (IC50); PARP14: 35.914 μM (IC50); PARP15: 51.623 nM (IC50)
[References]

[1] Sun Y, et al. YCH1899, a Highly Effective Phthalazin-1(2H)-one Derivative That Overcomes Resistance to Prior PARP Inhibitors. J Med Chem. 2023 Aug 21. DOI:10.1021/acs.jmedchem.3c00821
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