WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 408037
Description: ZT-12-037-01 is a potent, selective, ATP-competitive STK19 inhibitor. ZT-12-037-01 effectively blocks oncogenic NRAS-driven melanocyte malignant transformation and melanoma growth in vitro and in vivo.
MedKoo Cat#: 408037
Chemical Formula: C21H31N5O2
Exact Mass: 385.2478
Molecular Weight: 385.512
Elemental Analysis: C, 65.43; H, 8.11; N, 18.17; O, 8.30
Synonym: ZT-12-037-01; ZT-12-03701; ZT-12-037 01; ZT-12037-01; ZT-1203701; ZT-12037 01; ZT-1203701; ZT-1203701; ZT-1203701;
IUPAC/Chemical Name: N2-cyclopropyl-N4-(1-isopropylpiperidin-4-yl)-6,7-dimethoxyquinazoline-2,4-diamine
InChi Key: AMAQJTHMSLYMFT-UHFFFAOYSA-N
InChi Code: 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)
SMILES Code: COC1=CC2=NC(NC3CC3)=NC(NC4CCN(C(C)C)CC4)=C2C=C1OC
Activating mutations in NRAS account for 20%-30% of melanoma, but despite decades of research and in contrast to BRAF, no effective anti-NRAS therapies have been forthcoming. Here, we identify a previously uncharacterized serine/threonine kinase STK19 as a novel NRAS activator. STK19 phosphorylates NRAS to enhance its binding to its downstream effectors and promotes oncogenic NRAS-mediated melanocyte malignant transformation. A recurrent D89N substitution in STK19 whose alterations were identified in 25% of human melanomas represents a gain-of-function mutation that interacts better with NRAS to enhance melanocyte transformation. STK19D89N knockin leads to skin hyperpigmentation and promotes NRASQ61R-driven melanomagenesis in vivo.