| Identification | Back Directory | [Name]
3-Butyn-2-ol, 4-[3-[[[2-amino-5-[2-(1-methyl-4-piperidinyl)-5-thiazolyl]-3-pyridinyl]oxy]methyl]phenyl]-2-methyl- | [CAS]
2380300-79-6 | [Synonyms]
ZYF0033
HPK1-IN-22
ZYF0033 (Synonyms: HPK1-IN-22)
4-(3-(((2-amino-5-(2-(1-methylpiperidin-4-yl)thiazol-5-yl)pyridin-3-yl)oxy)methyl)phenyl)-2-methylbut-3-yn-2-ol
3-Butyn-2-ol, 4-[3-[[[2-amino-5-[2-(1-methyl-4-piperidinyl)-5-thiazolyl]-3-pyridinyl]oxy]methyl]phenyl]-2-methyl- | [Molecular Formula]
C26H30N4O2S | [MDL Number]
MFCD33398861 | [MOL File]
2380300-79-6.mol | [Molecular Weight]
462.61 |
| Chemical Properties | Back Directory | [Boiling point ]
647.3±55.0 °C(Predicted) | [density ]
1.29±0.1 g/cm3(Predicted) | [form ]
Solid | [pka]
13.05±0.29(Predicted) | [color ]
White to off-white |
| Hazard Information | Back Directory | [Uses]
ZYF0033 is an orally active inhibitor of the hematopoietic progenitor cell kinase HPK1 with an IC50 of less than 10 nM based on the phosphorylation inhibition of MBP protein. ZYF0033 promotes anti-cancer immune responses and reduces phosphorylation of SLP76 (serine 376). ZYF0033 inhibits tumor growth in the 4T-1 syngeneic mouse model and leads to increased intratumoral infiltration of DCs, NK cells, and CD107a+CD8+ T cells, but not T cells, PD-1+CD8+ T cells, TIM-3+CD8+ Infiltration of T cells and LAG3+CD8+ T cells was reduced[1][2]. | [in vivo]
The maximum tolerated dose of ZYF0033 exceeds 50 mg/kg (daily; po) and exceeds 120 mg/kg in a 6-day toxicity study. In the 4T-1 syngeneic mouse model, ZYF0033 regulates immune cell subsets, increases DC and NK cell infiltration, and promotes anti-cancer immune response[1].
| [IC 50]
HPK1: <10 nM (IC50) | [References]
[1] Si J, et al. Hematopoietic Progenitor Kinase1 (HPK1) Mediates T Cell Dysfunction and Is a Druggable Target for T Cell-Based Immunotherapies. Cancer Cell. 2020 Oct 12;38(4):551-566.e11. DOI:10.1016/j.ccell.2020.08.001
[2] Jingwen Si, et al. Hematopoietic Progenitor Kinase1 (HPK1) Mediates T Cell Dysfunction and Is a Druggable Target for T Cell-Based Immunotherapies. Cancer Cell. 2020 Oct 12;38(4):551-566.e11. |
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