pkmyt1

Lunresertib (RP-6306) is a potent, selective, and orally active PKMYT1 inhibitor with an IC50 of 14 nM. Lunresertib (RP-6306) inhibits the growth of CCNE1-amplified tumor cells in several preclinical xenograft models.

GSK-1520489A is an active PKMYT1 inhibitor.

PKMYT1-IN-8 (Compound 137) is an inhibitor of PKMYT1, with an IC50 value of 9 nM. It also inhibits EPHB3, EPHA1, KIT, EPHB1, EPHA2, EPHA3, and EPHB2, exhibiting IC50 values of 1.79, 3.17, 4.29, 6.32, 6.83, 8.10, and 10.9 μM, respectively. Additionally, PKMYT1-IN-8 suppresses the proliferation of cancer cells OVCAR3 with a GI50 of 2.02 μM.

WEE1/PKMYT1-IN-1 (compound 75) is an effective and orally bioavailable inhibitor of WEE1 and PKMYT1. It demonstrates antiproliferative activity.

PKMYT1-IN-9 is a highly selective, orally active inhibitor of PKMYT1 with an IC50 of 4.4 nM. It exhibits greater selectivity for PKMYT1 compared to WEE1, for which the IC50 is 32.4 μM. Additionally, PKMYT1-IN-9 demonstrates antitumor activity.

PKMYT1-IN-7 (compound 7) is an orally active PKMYT1 inhibitor with IC50 values of 1.6 nM for PKMYT1 and 0.06 μM for pCDK1. It inhibits the phosphorylation of CDK1 at T14 and Y15 sites and exhibits anticancer activity both in vitro and in vivo.

PKMYT1-IN-10 is a selective PKMYT1 inhibitor with an IC50 of 3 nM. It suppresses colony formation, induces apoptosis, and causes cancer cell cycle arrest in the S phase. This compound exhibits excellent hepatic microsomal and plasma stability with minimal inhibition of CYPs. PKMYT1-IN-10 is applicable for research in ovarian and breast cancer.

WEE1/PKMYT1-IN-2 is the axial chiral P configuration of WEE1/PKMYT1-IN-1. WEE1/PKMYT1-IN-1 is an effective and orally bioavailable inhibitor of WEE1 and PKMYT1, exhibiting antiproliferative activity.

PKMYT1-IN-13 is a potent, orally active, and highly selective PKMYT1 inhibitor. It exhibits an IC50 value of less than 10.0 nM for PKMYT1 in ADP-Glo assays and 19.9 nM in NanoBRET cell assays, demonstrating significant selectivity over WEE1. This compound shows selective antiproliferative activity in CCNE1-amplified cells with minimal impact on wild-type cells. Furthermore, PKMYT1-IN-13 demonstrates notable antitumor activity in HCC1569 mouse xenograft models and is applicable for studying CCNE1-amplified cancers such as gastric, ovarian, and breast cancers.

PKMYT1-IN-12 (Compound 4) is a selective inhibitor of PKMYT1 with an IC₅₀ of 2.6 nM. It effectively inhibits the phosphorylation of CDK1, demonstrating an IC₅₀ of 44 nM. PKMYT1-IN-12 serves as a target protein ligand useful in synthesizing PROTACD16-M1P2.

PKMYT1-IN-1 (Compound 1), a potent inhibitor of the membrane-associated tyrosine and threonine kinase (PKMYT1), exhibits an IC 50 of 8.8 nM. This compound effectively inhibits the proliferation of the tumor cell line HCC1569, with an IC 50 of 42 nM [1].

PKMYT1-IN-2 (compound 2) serves as a powerful inhibitor of PKMYT1, exhibiting an IC 50 of 5.7 nM. Additionally, it effectively suppresses the proliferation of HCC1569 cells with an IC 50 of 22 nM [1].

PKMYT1-IN-3 (compound 8ma) is a potent, selective inhibitor of PKMYT1, demonstrating an IC50 of 16.5 nM and exhibiting antitumor activity.

PKMYT1-IN-6 (compound 98) is an inhibitor of PKMYT1, exhibiting an IC50 of less than 50nM.

PKMYT1-IN-4 (compound 27) functions as a PKMYT1 inhibitor with an IC50 value under 50 nM.

PD-166285 is an inhibitor of PKMYT1 with an IC50 value of 17 nM. It exhibits potent antiproliferative effects on CCNE1-amplified OVCAR3 cells (IC50 = 0.14 μM) and HCC1569 cells (IC50 = 0.21 μM). PD-166285 can induce apoptosis and cause CCNE1-amplified HCC1569 cells to arrest at the G1/S phase of the cell cycle. This compound is applicable for research on PKMYT1-targeted CCNE1-amplified cancers.

XH-30 is a potent, selective, and orally active PKMYT1 inhibitor with an IC50 of 4.1 nM. It suppresses the proliferation of P53-mutated triple-negative breast cancer (TNBC) cells by inducing G2/M phase release, DNA damage, and apoptosis. In the MDA-MB-231 mouse model, XH-30 demonstrates antitumor activity and can be used in studies of P53-mutated TNBC.

PROTACD16-M1P2 is an orally active PKMYT1 PROTAC degrader with a DC50 of 0.7 nM. It also exhibits inhibitory activity against PKMYT1 with an IC50 of 7.6 nM and inhibits pCDK1 with an IC50 of 9 nM. PROTACD16-M1P2 demonstrates significant antitumor activity in mouse models and is applicable for breast cancer research.

(R)-Lunresertib (compound 183) is the enantiomer of the PKMYT1 inhibitor RP-6306. (R)-Lunresertib exhibits weak inhibitory activity, with an IC₅₀ of 1360 nM against PKMYT1.

Myt1-IN-4 (21) is an orally active, selective inhibitor of membrane-associated tyrosine- and threonine-specific cdc2 inhibitory kinase (Myt1) (Gene name PKMYT1), with an IC50 value of 2.6 nM. It exhibits antitumor properties.