1418143-09-5
Chemical Structure
Nuvisertib hydrochloride
Synonym(s): TP-3654 hydrochloride
- CAS No.: 1418143-09-5
- Formula:C22H26ClF3N4O
- Molecular Weight:454.92
IUPAC Name: 2-((1r,4r)-4-((3-(3-(trifluoromethyl)phenyl)imidazo[1,2-b]pyridazin-6-yl)amino)cyclohexyl)propan-2-ol hydrochloride
InChIKey: RJXWMEFBAZTYCY-BFLZMHAMSA-N
SMILES: FC(F)(F)C1=CC=CC(C2=CN=C(C=C3)N2N=C3N[C@H]4CC[C@@H](CC4)C(C)(O)C)=C1.Cl
Biological Activity: Nuvisertib hydrochloride (TP-3654 hydrochloride) is an orally active second-generation pan-PIM kinase inhibitor with Ki values of 5 nM, 239 nM, and 42 nM against PIM-1, PIM-2, and PIM-3, respectively. Nuvisertib hydrochloride inhibits JAK-independent inflammatory and survival signaling pathways, reduces the production of proinflammatory cytokines, restores apoptotic sensitivity, inhibits mTORC1, MYC, and TGF-β signaling pathways, and decreases the expression of fibrosis markers. Nuvisertib hydrochloride selectively impairs the transport function of ABCG2, resensitizes multidrug-resistant cancer cells to cytotoxic drugs, and overcomes JAK2 inhibitor resistance. Nuvisertib hydrochloride can be used in research related to myelofibrosis, renal cell carcinoma, multidrug-resistant cancer, advanced solid tumors, urothelial carcinoma, and prostate adenocarcinoma[1][2][3][4][5][6][7][8].
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Nuvisertib hydrochloride | Nuvisertib hydrochloride (TP-3654 hydrochloride) is an orally active second-generation pan-PIM kinase inhibitor with Ki values of 5 nM, 239 nM, and 42 nM against PIM-1, PIM-2, and PIM-3, respectively. Nuvisertib hydrochloride inhibits JAK-independent inflammatory and survival signaling pathways, reduces the production of proinflammatory cytokines, restores apoptotic sensitivity, inhibits mTORC1, MYC, and TGF-β signaling pathways, and decreases the expression of fibrosis markers. Nuvisertib hydrochloride selectively impairs the transport function of ABCG2, resensitizes multidrug-resistant cancer cells to cytotoxic drugs, and overcomes JAK2 inhibitor resistance. Nuvisertib hydrochloride can be used in research related to myelofibrosis, renal cell carcinoma, multidrug-resistant cancer, advanced solid tumors, urothelial carcinoma, and prostate adenocarcinoma. | |||||||||||||||||||||
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References
- [1]. Abruzzese E, et al. The Path Forward in MF: Small Molecules in the Limelight. Cancers (Basel). 2026 Apr 25;18(9):1370.
- [2]. El Chaer F, et al. Nuvisertib (TP-3654), an investigational selective PIM1 kinase inhibitor, showed durable clinical response and sustained hematological improvement in relapsed/refractory myelofibrosis patients. Blood. 2024;144(Suppl 1):655.
- [3]. Mascarenhas J, et al. Preliminary data from the Phase I/II study of nuvisertib, an oral investigational selective PIM1 inhibitor, in combination with momelotinib showed clinical responses in patients with relapsed/refractory myelofibrosis. Blood. 2025;146(Suppl 1):482. Abstract 634A.
- [4]. Meza KS, et al. Abstract 3174: Nuvisertib (TP‑3654) and Dordaviprone (ONC201) synergize to reduce renal cell carcinoma cell viability. Cancer Res. 2026;86(7_Supplement):3174.
- [5]. Dutta A, et al. Genetic ablation of Pim1 or pharmacologic inhibition with TP-3654 ameliorates myelofibrosis in murine models. Leukemia. 2022 Mar;36(3):746-759.
- [6]. Wu CP, et al. The Second-Generation PIM Kinase Inhibitor TP-3654 Resensitizes ABCG2-Overexpressing Multidrug-Resistant Cancer Cells to Cytotoxic Anticancer Drugs. International journal of molecular sciences. 2021 Aug 30;22(17):9440.
- [7]. Foulks JM, et al. A small-molecule inhibitor of PIM kinases as a potential treatment for urothelial carcinomas. Neoplasia. 2014 May;16(5):403-12. [Content Brief]
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[8]. Nath D, et al. The PIM Kinase Inhibitor TP‑3654 in Combination with Ruxolitinib Exhibits Marked Improvement of Myelofibrosis in Murine Models. Blood. 2018;132(Suppl 1):54. Abstract 635.
