(+)SHIN2 是一种丝氨酸羟甲基转移酶 (SHMT) 抑制剂，它的体内靶点能够用13C 丝氨酸示踪。(+)SHIN2 增加 Notch1 驱动的小鼠患原发性急性T淋巴细胞白血病 (T-ALL) 的存活率，并与 Methotrexate (HY-14519) 有协同作用。
| 生物活性 | (+)SHIN2 is aserine hydroxymethyltransferase(SHMT) inhibitor, whose target can be traced with13C-serine. (+)SHIN2 increases survival in NOTCH1-driven mouse primary acute lymphoblastic leukemia (T-ALL) in vivo with a synergistic effect withMethotrexate(HY-14519)[1]. |
| IC50& Target | Serine hydroxymethyltransferase (SHMT)[1] |
体外研究
(In Vitro) | (+)SHIN2 (0-10 μM; 24 h) blocks proliferation of HCT116 Ras-driven colon cancer cells, in a stereoselective manner with an IC50value of 300 nM[1].
(+)SHIN2 (0-100 μM; 48 h) achieves a nearly complete blockade of SHMT activity as evidenced by the decrease in M+1 and M+2 serine, M+2 glycine, and the incorporation of serine-derived glycine and 1C units into ATP, GTP, and dTTP (M+1-M+4 ATP and GTP and M+1 dTTP), and inhibits human T-ALL cell line Molt4 growth with a IC50value of 89 nM[1].
(+)SHIN2 (2 μM; 24 h) arrests cell cycle at S phase[1].
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体内研究
(In Vivo) | (+)SHIN2 (200 mg/kg; i.p.; single dose) shows therapeutic activity in mouse primary T-ALL in vivo[1].
| Animal Model: | Male C57BL/6 mice (10-14 weeks old) with mouse primary T-ALL[1] | | Dosage: | 200 mg/kg | | Administration: | Intraperitoneal injection; prepared with 30 mM U-13C-Serine (0.1 μL/min/g; infusion by catheter implanted on the right jugular vein); tested at 8 hr after treatment | | Result: | Decreased thymus weight and cellularity, which normalized after treatment discontinuation.
Showed generally well tolerated activity with modest hematological toxicity. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |
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