JAK
Signaling Pathway Map
Research Area
Inhibitory Selectivity
Isoform-specific Inhibitors
JAK Products
| Catalog No. | Information | Product Use Citations | Product Validations |
|---|---|---|---|
| S1378 |
Ruxolitinib (INCB018424)Ruxolitinib (INCB018424) is the first potent, selective, JAK1/2 inhibitor to enter the clinic with IC50 of 3.3 nM/2.8 nM in cell-free assays, >130-fold selectivity for JAK1/2 versus JAK3. |
a, Phospho- and total STAT1 in MDA-MB-453 cells treated with abemaciclib with or without ruxolitinib for 7 days.
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| S5001 |
Tofacitinib (CP-690550) CitrateTofacitinib citrate (CP-690550 citrate) is a novel inhibitor of JAK with IC50 of 1 nM, 20 nM and 112 nM against JAK3, JAK2, and JAK1, respectively. |
CP-690550 reduced the severity of ischemic damage. (A) CP-690550 (10 μM) suppressed IL-17 production by cdT cells and activated memory T cells. cdT cells and CD4+ CD44+ memory T cells isolated from C5BL6J mice through flow cytometry were stimulated for 24 h with plate-bound monoclonal antibodies to CD3 (2 ng/ml) and CD28 (1 ng/ml) in the presence or absence of IL-23 (25 ng/ml). IL-17A production and IL-17A expression level were measured by quantitative RT-PCR (a) and ELISA (b). (B) CBF reduction after brain ischemia. (C) Time-dependent changes in neurological score. *p < 0.05. (D) Infarct volume as visualized through TTC staining on day 3 in CP-690550 (CP)- and vehicle-treated mice.
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| S2162 |
AZD1480AZD1480 is a novel ATP-competitive JAK2 inhibitor with IC50 of 0.26 nM in a cell-free assay, selectivity against JAK3 and Tyk2, and to a smaller extent against JAK1. Phase 1. |
bDNA analysis showing that the JAK1/2 inhibitors CYT387, AZD1480 and Baricitinib positively regulate UCP1 expression in PSC-WA. Values are mean ± s.d. of n = three biological replicates and differences from DMSO are significant for * P < 0.005. P values were calculated using the two-tailed paired Student's t-test.
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| S2736 |
Fedratinib (SAR302503, TG101348)Fedratinib (SAR302503, TG101348) is a selective inhibitor of JAK2 with IC50 of 3 nM in cell-free assays, 35- and 334-fold more selective for JAK2 versus JAK1 and JAK3. Phase 2. |
Colony-forming assay results showing that the Jak2 inhibitor TG101348 reduces CFU-GM colonies generated from mutant fetal liver R2 cells. Results from 4 independent control or mutant fetal livers treated with TG101348 or dimethylsulfoxide (DMSO) are shown (mean ?SD). ***P < .001.
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| S1134 |
AT9283AT9283 is a potent JAK2/3 inhibitor with IC50 of 1.2 nM/1.1 nM in cell-free assays; also potent to Aurora A/B, Abl(T315I). Phase 2. |
HEL cells were treated with 0.5, 1 or 5 uM of AT9283 or left untreated for 3 hrs. The expression and phosphorylation state of STAT5 (P-STAT5) and Jak2 (P-Jak2) was assessed by Western blot immunodetection.
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| S8804New |
PF-06700841PF-06700841 is a potent inhibitor of Tyk2 and Jak1 with IC50s of 23 nM, 17 nM, 77 nM for Tyk2, Jak1 and Jak2 respectively. It has appropriate in-family selectivity against JAK2 and JAK3. |
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| S8765New |
PF-04965842PF-04965842 is a potent JAK1 inhibitor with IC50s of 29 nM, 803 nM, > 10 000 nM and 1250 nM for JAK1, JAK2, JAK3 and tyrosine kinase (TYK) 2, respectively. |
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| S5917New |
SolcitinibSolcitinib is an inhibitor of JAK1 with an IC50 of 8-9 nM, and shows 11-, 55- and 23-fold selectivity over JAK2, JAK3 and TYK2, respectively. |
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| S5902New |
1,2,3,4,5,6-Hexabromocyclohexane1,2,3,4,5,6-Hexabromocyclohexane is a potent inhibitor of JAK2 tyrosine kinase autophosphorylation with IC50 value to be estimated in low micromolar range. |
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| S5903New |
JANEX-1JANEX-1 is a small molecule inhibitor of JAK3 that selectively inhibits JAK3 at an IC50 of 78 µM without altering the activity of JAK1 or JAK2, or any other protein tyrosine kinases (IC50 ≥ 350 µM). |
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| S5904New |
WHI-P97WHI-P97 is a potent inhibitor of JAK-3 with an estimated Ki value of 0.09 μM in modeling studies and a measured IC50 value of 2.5 μM in EGFR kinase inhibition assays. |
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| S5754New |
Baricitinib phosphateBaricitinib phosphate is a selective JAK1 and JAK2 inhibitor with IC50 of 5.9 nM and 5.7 nM, ~70 and ~10-fold selective versus JAK3 and Tyk2, no inhibition to c-Met and Chk2. |
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| S5243New |
Ruxolitinib PhosphateRuxolitinib Phosphate is the phosphate salt form of ruxolitinib, an orally bioavailable Janus-associated kinase (JAK) inhibitor with potential antineoplastic and immunomodulating activities. |
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| S7812New |
Itacitinib (INCB39110)Itacitinib(INCB39110) is an orally bioavailable inhibitor of Janus-associated kinase 1 (JAK1) with potential antineoplastic activity. |
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| S2219 |
Momelotinib (CYT387)Momelotinib (CYT387) is an ATP-competitive inhibitor of JAK1/JAK2 with IC50 of 11 nM/18 nM, ~10-fold selectivity versus JAK3. Phase 3. |
Shown are WT pan T cells (both CD4＋and CD8＋ T cells; CD4－T cells are CD8＋T cells) after drug treatment. |
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| S2789 |
Tofacitinib (CP-690550,Tasocitinib)Tofacitinib (CP-690550,Tasocitinib) is a novel inhibitor of JAK3 with IC50 of 1 nM in cell-free assays, 20- to 100-fold less potent against JAK2 and JAK1. |
(J) Western blotting analysis of HIF1α abundance in response to 100 nM tofacitinib. Quantification of HIF1α detected by Western blot is shown alongside, with data normalized to SMC1 intensity and HIF1α protein abundance in IL-2-maintained cytotoxic T lymphocytes.
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| S2796 |
WP1066WP1066 is a novel inhibitor of JAK2 and STAT3 with IC50 of 2.30 μM and 2.43 μM in HEL cells; shows activity to JAK2, STAT3, STAT5, and ERK1/2 not JAK1 and JAK3. Phase 1. |
BrdU assay for the proliferation of WP1066- treated UM1 and Tca8113 cells (P<0.05).
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| S2692 |
TG101209TG101209 is a selective JAK2 inhibitor with IC50 of 6 nM, less potent to Flt3 and RET with IC50 of 25 nM and 17 nM in cell-free assays, ~30-fold selective for JAK2 than JAK3, sensitive to JAK2V617F and MPLW515L/K mutations. |
EGFR-ERCC1 effect on survival. QGP1 cells were transfected with Scrambled, ERCC1, EGFR, or EGFR-ERCC1 siRNA. Following 48 hours of siRNA transfection, Scrambled siRNA and ERCC1 siRNA-transfected cells were treated with 1 umol/L gefitinib or 125 nmol/L NU7026 (DNAPK inhibitor), or both, while EGFR siRNA and EGFR-ERCC1 siRNA-transfected cells were treated with 125 nmol/L of NU7026 1 hour prior 4 Gy IR treatment. Survival of these cells was then assessed 72 hours following IR treatment via MTT assay. The graphs show percentage of survival from 3 independent experiments as compared with untreated control. Bars show SD. Asterisks show statistical significance (*,P < 0.05; **, P < 0.01; ***, P < 0.001; NS, nonsignificant).
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| S2179 |
Gandotinib (LY2784544)Gandotinib (LY2784544) is a potent JAK2 inhibitor with IC50 of 3 nM, effective in JAK2V617F, 8- and 20-fold selective versus JAK1 and JAK3. Phase 2. |
Relative expression of BCLXL, c-MYC, CCND1, MMP2 and VEGF in (A) HL60 cell line. Cells were treated with 1 µM of ruxolitinib, fedratinib, gandotinib or tofacitinib for 6 h. RE=1 for DMSO control. Asterix (*) denotes statistical significance (p<0.05). Error bars denotes±standard deviation. Each relative expression value was obtained from at least two biological experiments run in two technical repeats.
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| S2686 |
NVP-BSK805 2HClNVP-BSK805 2HCl is a potent and selective ATP-competitive JAK2 inhibitor with IC50 of 0.5 nM,>20-fold selectivity towards JAK1, JAK3 and TYK2. |
Co-treatment of NVP-BSK805 (BSK) and PF-4708671 (PF) induces Bim and PUMA expression. HCT116 and EJ cells were treated with 6 μm of BSK and 30 μm of PF for 36 h.
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| S2851 |
Baricitinib (LY3009104, INCB028050)Baricitinib (LY3009104, INCB028050) is a selective JAK1 and JAK2 inhibitor with IC50 of 5.9 nM and 5.7 nM in cell-free assays, ~70 and ~10-fold selective versus JAK3 and Tyk2, no inhibition to c-Met and Chk2. Phase 3. |
bDNA analysis showing that the JAK1/2 inhibitors CYT387, AZD1480 and Baricitinib positively regulate UCP1 expression in PSC-WA. Values are mean ± s.d. of n = three biological replicates and differences from DMSO are significant for * P < 0.005. P values were calculated using the two-tailed paired Student's t-test. |
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| S2214 |
AZ 960AZ 960 is a novel ATP competitive JAK2 inhibitor with IC50 and Ki of <3 nM and 0.45 nM, 3-fold selectivity of AZ960 for JAK2 over JAK3. |
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| S2806 |
CEP-33779CEP33779 is a selective JAK2 inhibitor with IC50 of 1.8 nM, >40- and >800-fold versus JAK1 and TYK2. |
Potentiation of the antitumor effects of vincristine by CEP-33779 in a KBv200 cell xenograft model in nude mice. (A) The changes in tumor volume with time after tumor cell implantation. (B) The photograph of tumor size was taken on the 21st day after implantation. The various treatments were as follows: (a) Control (vehicle alone); (b) Vincristine (q2d x 6, ip, 0.2 mg/kg); (c) CEP-33779 (q2d x 6, p.o, 30 mg/kg) and (d) Vincristine (q2d x 6, ip, 0.2 mg/kg) plus CEP-33779 (q2d ?6, p.o, 30 mg/kg, given an hour before Vincristine administration).
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| S8057 |
Pacritinib (SB1518)Pacritinib (SB1518) is a potent and selective inhibitor of Janus Kinase 2 (JAK2) and Fms-Like Tyrosine Kinase-3 (FLT3) with IC50s of 23 and 22 nM in cell-free assays, respectively. Phase 3. |
Phosphorylation of the CSF-1R targets indicated was examined by immunoblotting
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| S2867 |
WHI-P154WHI-P154 is a potent JAK3 inhibitor with IC50 of 1.8 μM, no activity against JAK1 or JAK2, also inhibits EGFR, Src, Abl, VEGFR and MAPK, prevents Stat3, but not Stat5 phosphorylation. |
The protein expressions of p-Stat3/Stat3, Wnt 3a, Notch 1, and the activation of the Wnt and Notch pathways (Cyclin D1 and Hes 1) were assessed by Western blotting and RT-PCR. The Western blotting results were normalized to β-actin or Histone 4 as the control. Cells were pretreated with WHI-P154 (2 μM) 2 h before adding IL-23 (50 ng/mL). IL-23 treatment (50 ng/mL, 24 h) activated Wnt/Notch signaling and the persistent phosphorylation level of Stat3 was maintained up to 24 h in TE-1 cells (left panel). Relative mRNA level of Cyclin D1 and Hes 1 were detected by RT-PCR in TE-1 cells (right panel). Compiled data were produced from three independent experiments. **p < 0.01.
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| S7036 |
XL019XL019 is a potent and selective JAK2 inhibitor with IC50 of 2.2 nM, exhibiting >50-fold selectivity over JAK1, JAK3 and TYK2. Phase 1. |
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| S2902 |
S-Ruxolitinib (INCB018424)S-Ruxolitinib is the chirality of INCB018424, which is the first potent, selective, JAK1/2 inhibitor to enter the clinic with IC50 of 3.3 nM/2.8 nM, >130-fold selectivity for JAK1/2 versus JAK3. Phase 3. |
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| S8004 |
ZM 39923 HClZM 39923 HCl is an JAK1/3 inhibitor with pIC50 of 4.4/7.1, almost no activity to JAK2 and modestly potent to EGFR; also found to be sensitive to transglutaminase. |
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| S8538 |
PF-06651600PF-06651600 is a potent and irreversible JAK3-selective inhibitor with an IC50 of 33.1 nM but without activity (IC50 > 10 000 nM) against JAK1, JAK2, and TYK2. |
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| S7650 |
Peficitinib (ASP015K, JNJ-54781532)Peficitinib (ASP015K, JNJ-54781532) is an orally bioavailable JAK inhibitor. Phase 3. |
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| S7605 |
Filgotinib (GLPG0634)Filgotinib (GLPG0634) is a selective JAK1 inhibitor with IC50 of 10 nM, 28 nM, 810 nM, and 116 nM for JAK1, JAK2, JAK3, and TYK2, respectively. Phase 2. |
Confocal microscopy showing BAFF in ductal epithelial structures within SG organoids from patients with sicca (Sc) or primary Sjögren's syndrome (SS). Nuclei were stained with DAPI (blue). Original magnification × 100.
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| S7541 |
Decernotinib (VX-509)Decernotinib (VX-509) is a potent and selective JAK3 inhibitor with Ki of 2.5 nM, >4-fold selectivity over JAK1, JAK2, and TYK2, respectively. Phase 2/3. |
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| S7144 |
BMS-911543BMS-911543 is a potent and selective inhibitor of JAK2 with IC50 of 1.1 nM, ~350-, 75- and 65-fold selective to JAK1, JAK3 and TYK2, respectively. Phase 1/2. |
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| S7259 |
FLLL32FLLL32 is a potent JAK2/STAT3 inhibitor with IC50 of <5 μM. |
Interleukin-6 (IL-6) secretion was inhibited by B7‐H4 silence through JAK2/signal transducer and activator of transcription 3 (STAT3) inactivation. (a) ELISA results showed that, compared with cells pretreated with control shRNA, B7‐H4 silence led to reduction of IL‐6 secretion. However, compared with cells pretreated with control shRNA and FLLL32, IL‐6 secretion in Eca109, TE1, and TE13 esophageal squamous cell carcinoma cells pretreated with B7‐H4 shRNA and FLLL32 was not significantly affected.
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| S2407 |
CurcumolCurcumol is a pure monomer isolated from Rhizoma Curcumaeis with antitumor activities. |
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| S7137 |
GLPG0634 analogueGLPG0634 analogue is a selective JAK1 inhibitor with IC50 of 10 nM, 28 nM, 810 nM, and 116 nM for JAK1, JAK2, JAK3, and TYK2, respectively. Phase 2. |
Western blots showing the expression of γ-globin after treatments with (F) GLPG0634.
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| S8195 |
Oclacitinib maleateOclacitinib(PF 03394197) is a novel inhibitor of JAK family members with IC50 ranging from 10 to 99 nM and JAK1-dependent cytokines with IC50 ranging from 36 to 249 nM. It does not inhibit a panel of 38 non-JAK kinases. |
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| S7634 |
Cerdulatinib (PRT062070, PRT2070)Cerdulatinib (PRT-062070) is an oral active, multi-targeted tyrosine kinase inhibitor with IC50 of 12 nM/6 nM/8 nM/0.5 nM and 32 nM for JAK1/JAK2/JAK3/TYK2 and Syk, respectively. Also inhibits 19 other tested kinases with IC50 less than 200 nM. |
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| S8541 |
FM-381FM-381 is a JAK3 specific reversible covalent inhibitor with IC50 of 127 pM for JAK3 and demonstrates 400-, 2,700- and 3,600-fold selectivity over JAK1, JAK2, and TYK2, respectively. |
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| S7119 |
Go6976Go6976 is a potent PKC inhibitor with IC50 of 7.9 nM, 2.3 nM, and 6.2 nM for PKC (Rat brain), PKCα, and PKCβ1, respectively. Also a potent inhibitor of JAK2 and Flt3. |
Go6976 abolished the anticalcification activity of CST by promoting the ossification of cultured VSMCs. Rat VSMCs werecultured in growth medium or calcification medium in the presence or absence of 10 7mol/L of CST or in calcification medium containing10 7mol/L of CST and pretreated with different doses of Go6976 (0.01, 0.1 and 0.5lmol/L) for 30 min. On day 7 (A, n=4) and 12 (B,n=4), VSMCs were harvested for the determination of ALP activity (A) using an ALP assay kit and calcium content (B) using the OCPCmethod. The VSMCs cultured with calcification medium containing 10 7mol/L of CST were pretreated with different doses of Go6976 (0.01and 0.1lmol/L) for 30 min. On day 6, VSMCs were harvested for the detection of expression of OCN (C, D, n=6). Data from at least threeindependent experiments are presented as the mean SEM, and representative images are shown.*P<.05 and †P<.01. Ctrl, control groupin vitro;b-GP,b-glycerophosphate group;b-GP+CST,b-glycerophosphate plus 10 7mol/L cortistatin group;b-GP+CST+Go6976,b-glycerophosphate plus 10 7mol/L cortistatin plus Go6976 group.
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| Catalog No. | Information | Product Use Citations | Product Validations |
|---|---|---|---|
| S1378 |
Ruxolitinib (INCB018424)Ruxolitinib (INCB018424) is the first potent, selective, JAK1/2 inhibitor to enter the clinic with IC50 of 3.3 nM/2.8 nM in cell-free assays, >130-fold selectivity for JAK1/2 versus JAK3. |
a, Phospho- and total STAT1 in MDA-MB-453 cells treated with abemaciclib with or without ruxolitinib for 7 days.
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| S5001 |
Tofacitinib (CP-690550) CitrateTofacitinib citrate (CP-690550 citrate) is a novel inhibitor of JAK with IC50 of 1 nM, 20 nM and 112 nM against JAK3, JAK2, and JAK1, respectively. |
CP-690550 reduced the severity of ischemic damage. (A) CP-690550 (10 μM) suppressed IL-17 production by cdT cells and activated memory T cells. cdT cells and CD4+ CD44+ memory T cells isolated from C5BL6J mice through flow cytometry were stimulated for 24 h with plate-bound monoclonal antibodies to CD3 (2 ng/ml) and CD28 (1 ng/ml) in the presence or absence of IL-23 (25 ng/ml). IL-17A production and IL-17A expression level were measured by quantitative RT-PCR (a) and ELISA (b). (B) CBF reduction after brain ischemia. (C) Time-dependent changes in neurological score. *p < 0.05. (D) Infarct volume as visualized through TTC staining on day 3 in CP-690550 (CP)- and vehicle-treated mice.
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| S2162 |
AZD1480AZD1480 is a novel ATP-competitive JAK2 inhibitor with IC50 of 0.26 nM in a cell-free assay, selectivity against JAK3 and Tyk2, and to a smaller extent against JAK1. Phase 1. |
bDNA analysis showing that the JAK1/2 inhibitors CYT387, AZD1480 and Baricitinib positively regulate UCP1 expression in PSC-WA. Values are mean ± s.d. of n = three biological replicates and differences from DMSO are significant for * P < 0.005. P values were calculated using the two-tailed paired Student's t-test.
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| S2736 |
Fedratinib (SAR302503, TG101348)Fedratinib (SAR302503, TG101348) is a selective inhibitor of JAK2 with IC50 of 3 nM in cell-free assays, 35- and 334-fold more selective for JAK2 versus JAK1 and JAK3. Phase 2. |
Colony-forming assay results showing that the Jak2 inhibitor TG101348 reduces CFU-GM colonies generated from mutant fetal liver R2 cells. Results from 4 independent control or mutant fetal livers treated with TG101348 or dimethylsulfoxide (DMSO) are shown (mean ?SD). ***P < .001.
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| S1134 |
AT9283AT9283 is a potent JAK2/3 inhibitor with IC50 of 1.2 nM/1.1 nM in cell-free assays; also potent to Aurora A/B, Abl(T315I). Phase 2. |
HEL cells were treated with 0.5, 1 or 5 uM of AT9283 or left untreated for 3 hrs. The expression and phosphorylation state of STAT5 (P-STAT5) and Jak2 (P-Jak2) was assessed by Western blot immunodetection.
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| S8804New |
PF-06700841PF-06700841 is a potent inhibitor of Tyk2 and Jak1 with IC50s of 23 nM, 17 nM, 77 nM for Tyk2, Jak1 and Jak2 respectively. It has appropriate in-family selectivity against JAK2 and JAK3. |
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| S8765New |
PF-04965842PF-04965842 is a potent JAK1 inhibitor with IC50s of 29 nM, 803 nM, > 10 000 nM and 1250 nM for JAK1, JAK2, JAK3 and tyrosine kinase (TYK) 2, respectively. |
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| S5917New |
SolcitinibSolcitinib is an inhibitor of JAK1 with an IC50 of 8-9 nM, and shows 11-, 55- and 23-fold selectivity over JAK2, JAK3 and TYK2, respectively. |
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| S5902New |
1,2,3,4,5,6-Hexabromocyclohexane1,2,3,4,5,6-Hexabromocyclohexane is a potent inhibitor of JAK2 tyrosine kinase autophosphorylation with IC50 value to be estimated in low micromolar range. |
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| S5903New |
JANEX-1JANEX-1 is a small molecule inhibitor of JAK3 that selectively inhibits JAK3 at an IC50 of 78 µM without altering the activity of JAK1 or JAK2, or any other protein tyrosine kinases (IC50 ≥ 350 µM). |
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| S5904New |
WHI-P97WHI-P97 is a potent inhibitor of JAK-3 with an estimated Ki value of 0.09 μM in modeling studies and a measured IC50 value of 2.5 μM in EGFR kinase inhibition assays. |
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| S5754New |
Baricitinib phosphateBaricitinib phosphate is a selective JAK1 and JAK2 inhibitor with IC50 of 5.9 nM and 5.7 nM, ~70 and ~10-fold selective versus JAK3 and Tyk2, no inhibition to c-Met and Chk2. |
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| S5243New |
Ruxolitinib PhosphateRuxolitinib Phosphate is the phosphate salt form of ruxolitinib, an orally bioavailable Janus-associated kinase (JAK) inhibitor with potential antineoplastic and immunomodulating activities. |
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| S7812New |
Itacitinib (INCB39110)Itacitinib(INCB39110) is an orally bioavailable inhibitor of Janus-associated kinase 1 (JAK1) with potential antineoplastic activity. |
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| S2219 |
Momelotinib (CYT387)Momelotinib (CYT387) is an ATP-competitive inhibitor of JAK1/JAK2 with IC50 of 11 nM/18 nM, ~10-fold selectivity versus JAK3. Phase 3. |
Shown are WT pan T cells (both CD4＋and CD8＋ T cells; CD4－T cells are CD8＋T cells) after drug treatment. |
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| S2789 |
Tofacitinib (CP-690550,Tasocitinib)Tofacitinib (CP-690550,Tasocitinib) is a novel inhibitor of JAK3 with IC50 of 1 nM in cell-free assays, 20- to 100-fold less potent against JAK2 and JAK1. |
(J) Western blotting analysis of HIF1α abundance in response to 100 nM tofacitinib. Quantification of HIF1α detected by Western blot is shown alongside, with data normalized to SMC1 intensity and HIF1α protein abundance in IL-2-maintained cytotoxic T lymphocytes.
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| S2796 |
WP1066WP1066 is a novel inhibitor of JAK2 and STAT3 with IC50 of 2.30 μM and 2.43 μM in HEL cells; shows activity to JAK2, STAT3, STAT5, and ERK1/2 not JAK1 and JAK3. Phase 1. |
BrdU assay for the proliferation of WP1066- treated UM1 and Tca8113 cells (P<0.05).
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| S2692 |
TG101209TG101209 is a selective JAK2 inhibitor with IC50 of 6 nM, less potent to Flt3 and RET with IC50 of 25 nM and 17 nM in cell-free assays, ~30-fold selective for JAK2 than JAK3, sensitive to JAK2V617F and MPLW515L/K mutations. |
EGFR-ERCC1 effect on survival. QGP1 cells were transfected with Scrambled, ERCC1, EGFR, or EGFR-ERCC1 siRNA. Following 48 hours of siRNA transfection, Scrambled siRNA and ERCC1 siRNA-transfected cells were treated with 1 umol/L gefitinib or 125 nmol/L NU7026 (DNAPK inhibitor), or both, while EGFR siRNA and EGFR-ERCC1 siRNA-transfected cells were treated with 125 nmol/L of NU7026 1 hour prior 4 Gy IR treatment. Survival of these cells was then assessed 72 hours following IR treatment via MTT assay. The graphs show percentage of survival from 3 independent experiments as compared with untreated control. Bars show SD. Asterisks show statistical significance (*,P < 0.05; **, P < 0.01; ***, P < 0.001; NS, nonsignificant).
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| S2179 |
Gandotinib (LY2784544)Gandotinib (LY2784544) is a potent JAK2 inhibitor with IC50 of 3 nM, effective in JAK2V617F, 8- and 20-fold selective versus JAK1 and JAK3. Phase 2. |
Relative expression of BCLXL, c-MYC, CCND1, MMP2 and VEGF in (A) HL60 cell line. Cells were treated with 1 µM of ruxolitinib, fedratinib, gandotinib or tofacitinib for 6 h. RE=1 for DMSO control. Asterix (*) denotes statistical significance (p<0.05). Error bars denotes±standard deviation. Each relative expression value was obtained from at least two biological experiments run in two technical repeats.
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| S2686 |
NVP-BSK805 2HClNVP-BSK805 2HCl is a potent and selective ATP-competitive JAK2 inhibitor with IC50 of 0.5 nM,>20-fold selectivity towards JAK1, JAK3 and TYK2. |
Co-treatment of NVP-BSK805 (BSK) and PF-4708671 (PF) induces Bim and PUMA expression. HCT116 and EJ cells were treated with 6 μm of BSK and 30 μm of PF for 36 h.
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| S2851 |
Baricitinib (LY3009104, INCB028050)Baricitinib (LY3009104, INCB028050) is a selective JAK1 and JAK2 inhibitor with IC50 of 5.9 nM and 5.7 nM in cell-free assays, ~70 and ~10-fold selective versus JAK3 and Tyk2, no inhibition to c-Met and Chk2. Phase 3. |
bDNA analysis showing that the JAK1/2 inhibitors CYT387, AZD1480 and Baricitinib positively regulate UCP1 expression in PSC-WA. Values are mean ± s.d. of n = three biological replicates and differences from DMSO are significant for * P < 0.005. P values were calculated using the two-tailed paired Student's t-test. |
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| S2214 |
AZ 960AZ 960 is a novel ATP competitive JAK2 inhibitor with IC50 and Ki of <3 nM and 0.45 nM, 3-fold selectivity of AZ960 for JAK2 over JAK3. |
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| S2806 |
CEP-33779CEP33779 is a selective JAK2 inhibitor with IC50 of 1.8 nM, >40- and >800-fold versus JAK1 and TYK2. |
Potentiation of the antitumor effects of vincristine by CEP-33779 in a KBv200 cell xenograft model in nude mice. (A) The changes in tumor volume with time after tumor cell implantation. (B) The photograph of tumor size was taken on the 21st day after implantation. The various treatments were as follows: (a) Control (vehicle alone); (b) Vincristine (q2d x 6, ip, 0.2 mg/kg); (c) CEP-33779 (q2d x 6, p.o, 30 mg/kg) and (d) Vincristine (q2d x 6, ip, 0.2 mg/kg) plus CEP-33779 (q2d ?6, p.o, 30 mg/kg, given an hour before Vincristine administration).
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| S8057 |
Pacritinib (SB1518)Pacritinib (SB1518) is a potent and selective inhibitor of Janus Kinase 2 (JAK2) and Fms-Like Tyrosine Kinase-3 (FLT3) with IC50s of 23 and 22 nM in cell-free assays, respectively. Phase 3. |
Phosphorylation of the CSF-1R targets indicated was examined by immunoblotting
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| S2867 |
WHI-P154WHI-P154 is a potent JAK3 inhibitor with IC50 of 1.8 μM, no activity against JAK1 or JAK2, also inhibits EGFR, Src, Abl, VEGFR and MAPK, prevents Stat3, but not Stat5 phosphorylation. |
The protein expressions of p-Stat3/Stat3, Wnt 3a, Notch 1, and the activation of the Wnt and Notch pathways (Cyclin D1 and Hes 1) were assessed by Western blotting and RT-PCR. The Western blotting results were normalized to β-actin or Histone 4 as the control. Cells were pretreated with WHI-P154 (2 μM) 2 h before adding IL-23 (50 ng/mL). IL-23 treatment (50 ng/mL, 24 h) activated Wnt/Notch signaling and the persistent phosphorylation level of Stat3 was maintained up to 24 h in TE-1 cells (left panel). Relative mRNA level of Cyclin D1 and Hes 1 were detected by RT-PCR in TE-1 cells (right panel). Compiled data were produced from three independent experiments. **p < 0.01.
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| S7036 |
XL019XL019 is a potent and selective JAK2 inhibitor with IC50 of 2.2 nM, exhibiting >50-fold selectivity over JAK1, JAK3 and TYK2. Phase 1. |
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| S2902 |
S-Ruxolitinib (INCB018424)S-Ruxolitinib is the chirality of INCB018424, which is the first potent, selective, JAK1/2 inhibitor to enter the clinic with IC50 of 3.3 nM/2.8 nM, >130-fold selectivity for JAK1/2 versus JAK3. Phase 3. |
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| S8004 |
ZM 39923 HClZM 39923 HCl is an JAK1/3 inhibitor with pIC50 of 4.4/7.1, almost no activity to JAK2 and modestly potent to EGFR; also found to be sensitive to transglutaminase. |
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| S8538 |
PF-06651600PF-06651600 is a potent and irreversible JAK3-selective inhibitor with an IC50 of 33.1 nM but without activity (IC50 > 10 000 nM) against JAK1, JAK2, and TYK2. |
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| S7650 |
Peficitinib (ASP015K, JNJ-54781532)Peficitinib (ASP015K, JNJ-54781532) is an orally bioavailable JAK inhibitor. Phase 3. |
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| S7605 |
Filgotinib (GLPG0634)Filgotinib (GLPG0634) is a selective JAK1 inhibitor with IC50 of 10 nM, 28 nM, 810 nM, and 116 nM for JAK1, JAK2, JAK3, and TYK2, respectively. Phase 2. |
Confocal microscopy showing BAFF in ductal epithelial structures within SG organoids from patients with sicca (Sc) or primary Sjögren's syndrome (SS). Nuclei were stained with DAPI (blue). Original magnification × 100.
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| S7541 |
Decernotinib (VX-509)Decernotinib (VX-509) is a potent and selective JAK3 inhibitor with Ki of 2.5 nM, >4-fold selectivity over JAK1, JAK2, and TYK2, respectively. Phase 2/3. |
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| S7144 |
BMS-911543BMS-911543 is a potent and selective inhibitor of JAK2 with IC50 of 1.1 nM, ~350-, 75- and 65-fold selective to JAK1, JAK3 and TYK2, respectively. Phase 1/2. |
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| S7259 |
FLLL32FLLL32 is a potent JAK2/STAT3 inhibitor with IC50 of <5 μM. |
Interleukin-6 (IL-6) secretion was inhibited by B7‐H4 silence through JAK2/signal transducer and activator of transcription 3 (STAT3) inactivation. (a) ELISA results showed that, compared with cells pretreated with control shRNA, B7‐H4 silence led to reduction of IL‐6 secretion. However, compared with cells pretreated with control shRNA and FLLL32, IL‐6 secretion in Eca109, TE1, and TE13 esophageal squamous cell carcinoma cells pretreated with B7‐H4 shRNA and FLLL32 was not significantly affected.
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| S2407 |
CurcumolCurcumol is a pure monomer isolated from Rhizoma Curcumaeis with antitumor activities. |
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| S7137 |
GLPG0634 analogueGLPG0634 analogue is a selective JAK1 inhibitor with IC50 of 10 nM, 28 nM, 810 nM, and 116 nM for JAK1, JAK2, JAK3, and TYK2, respectively. Phase 2. |
Western blots showing the expression of γ-globin after treatments with (F) GLPG0634.
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| S8195 |
Oclacitinib maleateOclacitinib(PF 03394197) is a novel inhibitor of JAK family members with IC50 ranging from 10 to 99 nM and JAK1-dependent cytokines with IC50 ranging from 36 to 249 nM. It does not inhibit a panel of 38 non-JAK kinases. |
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| S7634 |
Cerdulatinib (PRT062070, PRT2070)Cerdulatinib (PRT-062070) is an oral active, multi-targeted tyrosine kinase inhibitor with IC50 of 12 nM/6 nM/8 nM/0.5 nM and 32 nM for JAK1/JAK2/JAK3/TYK2 and Syk, respectively. Also inhibits 19 other tested kinases with IC50 less than 200 nM. |
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| S8541 |
FM-381FM-381 is a JAK3 specific reversible covalent inhibitor with IC50 of 127 pM for JAK3 and demonstrates 400-, 2,700- and 3,600-fold selectivity over JAK1, JAK2, and TYK2, respectively. |
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| S7119 |
Go6976Go6976 is a potent PKC inhibitor with IC50 of 7.9 nM, 2.3 nM, and 6.2 nM for PKC (Rat brain), PKCα, and PKCβ1, respectively. Also a potent inhibitor of JAK2 and Flt3. |
Go6976 abolished the anticalcification activity of CST by promoting the ossification of cultured VSMCs. Rat VSMCs werecultured in growth medium or calcification medium in the presence or absence of 10 7mol/L of CST or in calcification medium containing10 7mol/L of CST and pretreated with different doses of Go6976 (0.01, 0.1 and 0.5lmol/L) for 30 min. On day 7 (A, n=4) and 12 (B,n=4), VSMCs were harvested for the determination of ALP activity (A) using an ALP assay kit and calcium content (B) using the OCPCmethod. The VSMCs cultured with calcification medium containing 10 7mol/L of CST were pretreated with different doses of Go6976 (0.01and 0.1lmol/L) for 30 min. On day 6, VSMCs were harvested for the detection of expression of OCN (C, D, n=6). Data from at least threeindependent experiments are presented as the mean SEM, and representative images are shown.*P<.05 and †P<.01. Ctrl, control groupin vitro;b-GP,b-glycerophosphate group;b-GP+CST,b-glycerophosphate plus 10 7mol/L cortistatin group;b-GP+CST+Go6976,b-glycerophosphate plus 10 7mol/L cortistatin plus Go6976 group.
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