PIM3 Inhibitor

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.

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.

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.

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.

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.

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.

CDK6/PIM1-IN-1 is a potent and balanced dual CDK6/PIM1 inhibitor with IC₅₀ values of 39 and 88 nM, respectively. CDK6/PIM1-IN-1 inhibits CDK4 (IC₅₀=3.6 nM). CDK6/PIM1-IN-1 significantly inhibits acute myeloid leukemia (AML) cell proliferation, arrest cell cycle at the G1 phase, and promote cell apoptosis. CDK6/PIM1-IN-1 exhibits potent anti-AML activity.

GNE-955 is a potent and orally active pan Pim kinase inhibitor with K_is of 0.018, 0.11, 0.08 nM for Pim1, Pim2, Pim3, respectively.

VB1080 (compound 12) is a potent PIM inhibitor with IC₅₀ values of 69.5, 4996, 9.88 µM for PIM1, PIM2, PIM3, respectively. VB1080 shows cytotoxicity. VB1080 shows anthelmintic activity.

PIM3-IN-1 hydrochloride (Compound 19a) is an inhibitor of (PIM2/3), with the highest inhibition level being against PIM3, having an IC₅₀ value in the nanomolar range. PIM3-IN-1 hydrochloride can be used in cancer research.

Bufothionine is an alkaloid. Bufothionine can be isolated from Cinobufacini. Bufothionine induces mitochondria-mediated Apoptosis. Bufothionine significantly reduces serum IL-6 concentration, suppresses p-Stat3^tyr705, p-Stat3^ser727 and Jak2 expressions. Bufothionine upregulates Atg5, Atg7 and LC3Ⅱ expressions. Bufothionine induces Autophagy. Bufothionine suppresses PIM3 expression. Bufothionine relieves symptoms of H22-tumor-bearing mice and exerts anti-inflammation activity. Bufothionine exerts anti-cancer activities against gastric cancer.