ZT-12-037-01

ZT-12-037-01 is a STK19-targeted inhibitor with a high-affinity interaction with STK19 protein and inhibits oncogenic NRAS-driven melanocyte malignant transformation. It inhibited phosphorylation of NRAS (major isoform of Ras family) with IC50 value of 24nM.

Product information

CAS Number: 2328073-61-4

Molecular Weight: 385.50

Formula: C21H31N5O2

Chemical Name: N2-cyclopropyl-N4-(1-isopropylpiperidin-4-yl)-6,7-dimethoxyquinazoline-2,4-diamine

Smiles: CC(C)N1CCC(CC1)NC1=NC(NC2CC2)=NC2=CC(OC)=C(C=C12)OC

InChiKey: AMAQJTHMSLYMFT-UHFFFAOYSA-N

InChi: InChI=1S/C21H31N5O2/c1-13(2)26-9-7-15(8-10-26)22-20-16-11-18(27-3)19(28-4)12-17(16)24-21(25-20)23-14-5-6-14/h11-15H,5-10H2,1-4H3,(H2,22,23,24,25)

Technical Data

Appearance: Solid Power

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

Solubility: DMSO: 41 mg/mL(106.35 mM). Water: Insoluble.

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: ≥12 months 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:

ZT-12-037-01 treatment efficiently inhibits phosphorylation of NRAS in a dose- and time-dependent manner. Furthermore, with increasing ATP concentrations, the IC50 of ZT-12-037-01 against STK19 accordingly increased, indicating that ZT-12-037-01 is an ATP-competitive inhibitor for STK19. ZT-12-037-01 treatment significantly inhibits mutant NRAS-STK19-driven melanocyte colony formation, proliferation, and tumor formation. Pro-apoptotic effect of ZT-12-037-01 is dramatically enhanced in cells expressing oncogenic NRAS.

In Vivo:

ZT-12-037-01 is a highly potent STK19 inhibitor with low in vivo toxicity. Its treatment also inhibits growth of SK-MEL-2 xenograft melanoma (with NRASQ61R) in a dose-dependent manner.

References:

1. Yin C, et al. Cell. 2019, 176(5):1113-1127.

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