PIM1-IN-6 (compound 5h) is a potent PIM-1 inhibitor, with an IC50 of 0.60 μM. PIM1-IN-6 shows the high cytotoxicity activity against HCT-116 and MCF-7 cells, with IC50 values of 1.51 and 15.2 μM, respectively[1].
Quercetagetin (6-Hydroxyquercetin) is the major flavonoid isolated from Citrus unshiu (C. unshiu) peel[3]. Quercetagetin is a moderately potent and selective, cell-permeable pim-1 kinase inhibitor (IC50, 0.34 μM)[1]. Anti-inflammatory and anticancer properties.
R8-T198wt is a cell-permeable peptide inhibitor of Pim-1 kinase, derived from p27Kip1. R8-T198wt inhibits Pim-1 phosphorylation of p27Kip1 and Bad; induces cell cycle arrest (at G1) and apoptosis in DU145 prostate cancer cells. R8-T198wt also inhibits Pim-1-dependent growth of DU145 cells in vitro and in vivo. R8-T198wt displays no effect on the growth of normal prostate epithelial RPWE-1 cells at concentrations of 10 and 20 μM.
Pim-1/2 kinase inhibitor 1 is an orally active pim-1/2 kinase inhibitor. Pim-1/2 kinase inhibitor 1 blocks the ability of Pim kinases to phosphorylate peptides, and inhibits the pim protein kinase directed phosphorylation of 4E-BP1 and p27Kip1. Pim-1/2 kinase inhibitor 1 can be used in study of cancer, especially prostate cancer[1].
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[1].
M-110 is a novel and highly selective inhibitor of PIM kinases; inhibits the proliferation of prostate cancer cell lines with IC50s of 0.6 to 0.9 uM, with no activity on normal human peripheral blood mononuclear cells up to 40 uM.IC50 value:Target: Pim inhibitorin vitro: Treatment of DU-145 cells with M-110 or with a structurally unrelated PIM inhibitor, SGI-1776, significantly reduces pSTAT3Tyr705 expression without affecting the expression of STAT3. Furthermore, treatment of DU-145 cells with M-110 attenuates the interleukin-6–induced increase in pSTAT3Tyr705 [1]. M-110 treatment of APC-mutant DLD-1 cells, preferentially attenuated constitutive TOPFLASH activity as compared with FOPFLASH, and had no effect on the CMV-β-galactosidase control reporter. In SW480 cells, M-110 also decreased the levels of free cytoplasmic β-catenin as determined by E-cadherin pull down assays. M-110 also blocked Wnt signaling when other destruction complex components were disrupted, including abrogation of AXIN1/2 expression using siRNAs or inhibition of GSK3β activity using LiCl or I3M [2].
Pim-1 kinase inhibitor 1 is a Pim-1 kinase inhibitor with an IC50 of 0.11 μM for Pim-1 kinase. Pim-1 kinase inhibitor 1 shows anticancer activity to several cancer cell lines by promotes cell apoptosis. Pim-1 kinase inhibitor 1 can be used for the research of cancer[1].
TP-3654 is a second-generation Pim kinase inhibitor with Ki values of 5 and 42 nM for Pim-1 and Pim-3, respectively.
PIM1-IN-2 is a potent and ATP competitive Pim-1 inhibitor with a Ki of 91 nM. PIM1-IN-2 targets the ATP-binding kinase hinge region not by forming classical hydrogen bonds[1].
Pim-1 kinase inhibitor 5 (Compound 4c) is a Pim-1 kinase inhibitor (IC50: 0.61 μM). Pim-1 kinase inhibitor 5 shows cytotoxicity against cancer cells, with IC50s of 6.95-20.19 μM for HepG2, MCF-7, PC3, and HCT-116 cells[1].
PIM447 is a pan-PIM kinase ihibitor with Kis of 6, 18, 9 nM for PIM1, PIM2 and PIM3, respectively.
SGI-1776 is an inhibitor of Pim kinases, with IC50s of 7 nM, 363 nM, and 69 nM for Pim-1, -2 and -3, respectively.
MNK/PIM-IN-1 represents an innovative dual MNK/PIM inhibitor with a good pharmacokinetic profile.
Pim-1 kinase inhibitor 6 (Compound 4d) is a potent Pim-1 kinase inhibitor with IC50 value of 0.46 μM, and has significant cytotoxic effect on cancer cells[1].
HJ-PI01 (10-Acetylphenoxazine) is an orally active Pim-2 inhibitor. HJ-PI01 induces apoptosis and autophagic cell death of cancer cells. HJ-PI01 inhibits tumor growth in MDA-MB-231 xenograft mice. HJ-PI01 can be used for cancer research[1].
GDC-0339 is a Pim kinase inhibitor with IC50 of 43.6 nM for BaF3 PIM1.IC50 value: 43.6 nM (for BaF3 PIM1), 0.04 nM (Ki, for PIM1 LC-3K)Target: Pim
GSK-3β inhibitor 13 (compound 47) is an orally active and potent GSK-3β inhibitor with blood-brain permeability. GSK-3β inhibitor 13 inhibits GSK-3β and GSK-3α with IC50s of 0.73 nM and 0.35 nM, respectively. GSK-3β inhibitor 13 significantly decreases the phosphorylation of tau (IC50=58 nM), which leads the formation of the neurofibrillary tangles associated with Alzheimer's disease[1].
CX-6258 hydrochloride hydrate is a potent, orally efficacious Pim 1/2/3 kinase(IC50=5 nM/25 nM/16 nM) inhibitor with excellent biochemical potency and kinase selectivity.IC50 Value: 5 nM/25 nM/16 nM (Pim 1/2/3) [1]Target: pan-Pimin vitro: CX-6258 inhibited Flt-3 and Pim-3 (IC50=0.134 and 0.016 uM). At 0.5 uM of CX-6258, only Pim-1, Pim-2, Pim-3, and Flt-3 of the 107 kinases tested were inhibited by more than 80%, showing excellent selectivity. CX-6258 was also shown to be a reversible inhibitor of Pim-1 (Ki=0.005 uM). CX-6258 showed robust antiproliferative potencies against all cell lines tested derived from human solid tumors and hematological malignancies. In mechanistic cellular assays with MV-4-11 human AML cells, (13) caused dose-dependent inhibition of the phosphorylation of 2 pro-survival proteins, Bad and 4E-BP1, at the Pim kinase specific sites S112 and S65 and T37/46, respectively[1]. Pim-1 inhibition using the small molecule inhibitor CX-6258 (12 mM, 3 h) diminishes endogenous NKX3.1 steady state levels in 22RV1 and LNCaP cells. CX-6258 treatment (12 mM, 3 h) treatment diminished steady-state levels of ectopic NKX3.1 in PC3 cells. CX-6258 treatment resulted in a significant reduction in NKX3.1 half-life. While ectopically expressed NKX3.1 in control cells had a half-life of _90 min, Pim-1 inhibition reduced the half-life to _52 min [2].in vivo: CX-6258 showed dose-dependent efficacy in mice bearing MV-4-11 xenografts, with 45% and 75% TGI at 50 and 100 mg/kg/day, respectively. Treatment of mice bearing PC3 xenografts with CX-6258 p.o. 50 mg/kg was also well tolerated and produced 51% TGI.
(Z)-SMI-4a is a selective ATP-competitive Pim-1 kinase inhibitor with an IC50 of 21 nM for Pim-1 compared to an IC50 of 100 nM for Pim-2 and with little or no activity against a panel of 50 other kinases tested.IC50 value: 21 nM (Pim1); 100 nM (Pim2) [1]Target: Pim-1in vitro: Incubation of pre-T-LBL cells with (Z)-SMI-4a induced G1 phase cell-cycle arrest secondary to a dose-dependent induction of p27(Kip1), apoptosis through the mitochondrial pathway, and inhibition of the mammalian target of rapamycin C1 (mTORC1) pathway based on decreases in phospho-p70 S6K and phospho-4E-BP1, 2 substrates of this enzyme. In addition, treatment of these cells with (Z)-SMI-4a was found to induce phosphorylation of extracellular signal-related kinase1/2 (ERK1/2), and the combination of (Z)-SMI-4a and a mitogen-activated protein kinase kinase 1/2 (MEK1/2) inhibitor was highly synergistic in killing pre-T-LBL cells [1]. Ectopic expression of phosphomimetic mutants of eIF4B conferred resistance to apoptosis by the Pim kinase inhibitor (Z)-SMI-4a in Abl-transformed cells [2].in vivo: In immunodeficient mice carrying subcutaneous pre-T-LBL tumors, treatment twice daily with (Z)-SMI-4a caused a significant delay in the tumor growth without any change in the weight, blood counts, or chemistries [1].
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[1].
HS56 (Pim-DAPK3 inhibitor HS56) is a potent, dual Pim/DAPK3 inhibitor with Ki of 72 nM (Pim-3) and 315 nM (DAPK3), shows micromolar potency toward Pim-1 and Pim-2 (Ki=1.5 and 17 uM); displays a high degree of selectivity for DAPKs and Pims against a panel of 468 kinases, with only two off-target interactions TYK2 and GAK; also displays no significant inhibition or activation of nicotinic, adrenergic, or muscarinic receptors at 10 uM; HS56 delayed force onset, decreased contractile force, and reduced LC20 phosphorylation in excised rat caudal arterial VSM tissues, lowers blood pressure in spontaneously hypertensive mice without affecting heart rate.
SEL24-B489 (SEL24) is a potent, dual PIM and FLT3-ITD inhibitor with Kd of 2/2/3 nM for PIM1/2/3, Kd of 160/16 nM for FLT3-WT/FLT3-ITD, respectively; exhibits significantly broader on-target activity in AML cell lines (MV-4-11 GI50=20 nM) and primary AML blasts than selective FLT3-ITD or PIM inhibitors, decreases viability of AML cells with FLT3-TKD mutations associated with resistance to selective FLT3-ITD inhibitors; inhibits the growth of a broad panel of AML cell lines in xenograft models. Blood Cancer Phase 2 Clinical
Pim1/AKK1-IN-1 is a potent multi-kinase inhibitor with Kd values of 35 nM/53 nM/75 nM/380 nM for Pim1/AKK1/MST2/LKB1 respectively, and also inhibits MPSK1 and TNIK.
CK2/ERK8-IN-1 is a dual casein kinase 2 (CK2) (Ki of 0.25 µM) and ERK8 inhibitor with IC50s of 0.50 μM. CK2/ERK8-IN-1 also binds to PIM1, HIPK2 (homeodomain-interacting protein kinase 2), and DYRK1A with Kis of 8.65 µM, 15.25 µM, and 11.9 µM, respectively. CK2/ERK8-IN-1 has pro-apoptotic efficacy[1].
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.
TCS-PIM-1-4a is a Pim inhibitor that blocks mTORC1 activity via activation of AMPK; kills a wide range of both myeloid and lymphoid cell lines (with IC50 values ranging from 0.8 to 40 μM).IC50 value:Target: Pim SMI-4a a novel benzylidene-thiazolidine-2, 4-dione small molecule inhibitor of the Pim kinases, kills a wide range of both myeloid and lymphoid cell lines with precursor T-cell lymphoblastic leukemia/lymphoma (pre-T-LBL/T-ALL) being highly sensitive. Incubation of pre-T-LBL cells with SMI-4a induced G1 phase cell-cycle arrest secondary to a dose-dependent induction of p27(Kip1), apoptosis through the mitochondrial pathway, and inhibition of the mammalian target of rapamycin C1 (mTORC1) pathway based on decreases in phospho-p70 S6K and phospho-4E-BP1, 2 substrates of this enzyme. In addition, treatment of these cells with SMI-4a was found to induce phosphorylation of extracellular signal-related kinase1/2 (ERK1/2), and the combination of SMI-4a and a mitogen-activated protein kinase kinase 1/2 (MEK1/2) inhibitor was highly synergistic in killing pre-T-LBL cells. SMI-4a blocked the rapamycin-sensitive mTORC1 activity by stimulating the phosphorylation and thus activating the mTORC1 negative regulator AMP-dependent protein kinase (AMPK).
CX-6258 hydrochloride is a potent and kinase selective pan-Pim kinases inhibitor, with IC50s of 5 nM, 25 nM and 16 nM for Pim-1, Pim-2 and Pim-3, respectively[1].
INCB053914 phosphate is an inhibitor of Pim extracted from patent WO 2017044730 A1, compound 1; has an IC50 of less than 35 nM.
TCS PIM-1 1(sc-204330) is a potent and selective ATP-competitive Pim-1 kianse inhibitor with IC50 of 50 nM, displays good selectivity over Pim-2 and MEK1/MEK2(IC50s >20,000 nM).IC50 value: 50 nM [1]Target: Pim-1TCS PIM-1 1 bound convincingly within the ATP-binding site of Pim-1 suggesting an ATP-competitive inhibitory mechanism. Preliminary data further suggested that 1 lacked in vitro inhibitory activity toward related serine/threonine kinases Pim-2 and MEK1/2 (IC50 > 20 lM). Hence, small molecules similar to TCS PIM-1 1 may serve as useful starting scaffolds for the development of other improved yet selective Pim-1 inhibitors.
FD1024 is PIM inhibitor (IC50s: 1.96, 38.9, 4.17 nM for PIM1, 2, 3). FD1024 can be used for research of acute myeloid leukemia. FD1024 has strong antiproliferative activity against the tested AML cell lines, with 0.16 μM, 0.12 μM, 1.05 μM, 1.39μM for EOL-1, MV-4-11, KG-1, MOLM-16 cells. FD1024 also has antitumor efficacy in mice[1].