PIM2 Inhibitor

AZD1208 is an orally bioavailable, highly selective PIM kinases inhibitor.

CRT0066101 dihydrochloride is a potent and orally active PKD inhibitor with IC₅₀ values of 1 nM, 2.5 nM and 2 nM for PKD1, PKD2, and PKD3, respectively. CRT0066101 dihydrochloride is also a potent PIM2 inhibitor with an IC₅₀ of ~135.7 nM. CRT0066101 dihydrochloride exhibits anti-inflammatory activity in mice LPS (HY-D1056)-induced lung injury models, and has anticancer effects.

SMI-4a (TCS-PIM-1-4a) is a poten, selective, cell-permeable and ATP-competitive Pim-1 inhibitor with an IC₅₀ of 24 μM and a K_i of 0.6 μM. SMI-4a also inhibits Pim-2 (IC₅₀ of 100 μM), and does not significantly inhibit the other serine/threonine- or tyrosine-kinases. SMI-4a has anticancer activity.

PIM447 (LGH447) is a potent, orally available, and selective pan-PIM kinase inhibitor, with K_i values of 6, 18, and 9 pM for PIM1, PIM2, and PIM3, respectively. PIM447 displays dual antimyeloma and bone-protective effects. PIM447 induces apoptosis.

CRT0066101 is a potent and orally active PKD inhibitor with IC₅₀ values of 1 nM, 2.5 nM and 2 nM for PKD1, PKD2, and PKD3, respectively. CRT0066101 is also a potent PIM2 inhibitor with an IC₅₀ of ~135.7 nM. CRT0066101 exhibits anti-inflammatory activity in mice LPS (HY-D1056)-induced lung injury models, and has anticancer effects.

VS-II-173 is a pan-Pim kinase inhibitor with IC₅₀ values ​​of 0.07 μM and 0.02 μM for Pim1 and Pim3, respectively, and a residual activity of 46% for Pim2 at 1 μM. VS-II-173 also inhibits kinases such as HIPK2, PRK2, RSK1, DYRK1a and AMPK_α1, selectively inhibiting acute myeloid leukemia (AML) cells with significantly lower toxicity to non-malignant cells (EC₅₀ > 30 μM). VS-II-173 weakens the phosphorylation of substrates such as Stat5 (Y694), MDM2 (S166), Bad (S112), and 4E-BP1 (T37/46) by inhibiting Pim kinase-mediated signaling pathways, blocking pro-survival signals in AML cells and inducing apoptosis. VS-II-173 synergistically enhances anti-AML activity when combined with Daunorubicin (HY-13062A). VS-II-173 can be used in AML research, especially for AML with FLT3-ITD mutations and NPM1 mutations .

FD2024 is a pan-PIM kinase inhibitor with IC₅₀ values of 0.17 nM, 1.86 nM, and 0.38 nM against PIM-1, PIM-2, and PIM-3, respectively. FD2024 induces cell apoptosis. FD2024 inhibits the phosphorylation of mTOR, p70S6K, S6, 4EBP1, and BAD proteins. FD2024 exhibits anti-acute myeloid leukemia activity. FD2024 can be used in studies related to acute myeloid leukemia.

Quercetagetin (6-Hydroxyquercetin) is a flavonoid. Quercetagetin is a moderately potent and selective, cell-permeable pim-1 kinase inhibitor (IC₅₀, 0.34 μM). Anti-inflammatory and anticancer properties.

PIM447 dihydrochloride (LGH447 dihydrochloride) is a potent, orally available, and selective pan-PIM kinase inhibitor, with K_i values of 6, 18, and 9 pM for PIM1, PIM2, and PIM3, respectively. PIM447 dihydrochloride displays dual antimyeloma and bone-protective effects. PIM447 dihydrochloride induces apoptosis.

GDC-0339 is a potent, orally bioavailable and well tolerated pan-Pim kinase inhibitor, with K_is of 0.03 nM, 0.1 nM and 0.02 nM for Pim1, Pim2 and Pim3, respectively. GDC-0339 is discovered as a potential treatment of multiple myeloma.

SMI-16a is a selective Pim kinase inhibitor with IC₅₀ values of 0.15, 0.02 and 48 μM for Pim1, Pim2 and PC3 cells, respectively.

Uzansertib (INCB053914) phosphate is an orally active, ATP-competitive pan-PIM kinase inhibitor with IC₅₀s of 0.24 nM, 30 nM, 0.12 nM for PIM1, PIM2, PIM3, respectively. Uzansertib phosphate has broad anti-proliferative activity against a variety of hematologic tumor cell lines.

SEL24-B489 is a potent, type I, orally active, dual PIM and FLT3-ITD inhibitor, with K_d values of 2 nM for PIM1, 2 nM for PIM2 and 3 nM for PIM3, respectively.

JP-11646 is a pan-PIM inhibitor with increased potency against PIM2 (IC₅₀ = 0.5 nM). JP11646 is freely reversible and ATP non-competitive. JP-11646 results in a decrease of PIM1, 2, and 3 mRNA. JP-11646 can effectively inhibit cell viability in small cell lung cancer (SCLC) and large cell neuroendocrine carcinomas of the lung (LCNEC). JP-11646 can cause a decrease in p-4EBP-1 protein, increasing the cleavage of caspases while decreasing caspase-3. JP-11646 induces apoptosis or necroptosis in cells. JP-11646 leads to reductions in MYC paralogs. JP-11646 can be used for the study of SCLC, LCNEC, human acute leukemia (AML), multiple myeloma (MM), and triple-negative breast cancer (TNBC).

HTH-01-091 is a potent and selective maternal embryonic leucine zipper kinase (MELK) inhibitor, with an IC₅₀ of 10.5 nM. HTH-01-091 also inhibits PIM1/2/3, RIPK2, DYRK3, smMLCK and CLK2. HTH-01-091 can be uesd for breast cancer research.

Uzansertib (INCB053914) is an orally active, ATP-competitive pan-PIM kinase inhibitor with IC₅₀s of 0.24 nM, 30 nM, 0.12 nM for PIM1, PIM2, PIM3, respectively. Uzansertib has broad anti-proliferative activity against a variety of hematologic tumor cell lines.

PIM1-IN-1 is a potent and highly selective PIM1/3 inhibitor, with IC₅₀s of 7, 5530 and 70 nM for PIM1, PIM2, and PIM3, respectively, inhibits the phosphorylation of BAD, a downstream target of PIM, with an EC₅₀ of 262 nM. PIM1-IN-1 shows no obvious effect on FLT3 or hERG binding. Antiproliferative and anti-cancer activity.

AZD1897 is a PIM1, PIM2, and PIM3 inhibitor with IC₅₀ values of less than 3 nM for these three PIM kinases. AZD1897 exhibits anticancer activity and synergistically inhibits the activity of acute myeloid leukemia (AML) cells in combination with Capivasertib (HY-15431). This synergistic inhibitory effect is achieved through the inhibition of the mTOR and MCL1 pathways.

AZD1208 hydrochloride is an orally bioavailable, highly selective PIM kinases inhibitor.

HS56 is an ATP-competitive dual Pim/DAPK3 inhibitor with K_i values of 0.26, 0.208, 2.94, and ＞100 μM for DAPK3, Pim-3, Pim-1, and Pim-2, respectively. HS56 inhibits LC20 phosphorylation and smooth muscle contraction. HS56 decreases blood pressure in spontaneously hypertensive mice. HS56 can be used in research of hypertension.