L-Histidinol (dihydrochloride)

L-Histidinol dihydrochloride is an orally active histidyl-tRNA synthetase inhibitor. L-Histidinol dihydrochloride interferes with the initiation stage of protein synthesis, thus affecting cell proliferation and metabolism. L-Histidinol dihydrochloride has the effect of modulating the sensitivity of tumor cells to chemotherapeutic agents. L-Histidinol dihydrochloride reduces the toxicity of certain chemotherapeutic agents to normal tissues and enhance the sensitivity of tumor cells to chemotherapeutic agents^{[1][2][3][4][5][6][7][8][9][10]}. In Vitro: L-histidinol (1-15 mM; 4 h pretreatment) dihydrochloride potentiates hyperthermic cell (HeLa and S-180)-killing in-vitro^[1].
L-histidinol (3 mM; 2 h) dihydrochloride inhibits protein and ribosomal RNA synthesis in mouse L cells^[2].
L-histidinol (1-3 mM; 24 h) dihydrochloride shows a modest, dose-dependent toxicity to cultured P815 mastocytoma cells^[3].
L-histidinol (3 mM; 48 h) dihydrochloride, when combined with different anticancer drugs, reverses the multidrug-resistance attribute of CH^RC5 cells^[4].
L-histidinol (1 mM; 24 h) dihydrochloride inhibits the proliferative responses induced by Con A and LPS (HY-D1056) in cultured mouse spleen cells^[5].
In Vivo: L-Histidinol (5 mg/injection; i.p.; administered at -2, 0, 2, 4, and 6 h) dihydrochloride, when combined with ara-C (HY-13605) or FUra, eliminates their bone marrow toxicity in DBA/2J mice and enhances the eradication of intraperitoneal P815 mastocytoma cells^[3].
L-Histidinol (250 mg/kg; i.p.) dihydrochloride, in combination with BCNU (HY-13585), improves the treatment effect of P388 leukemia in DBA/2J mice, increasing the median survival time and the number of 60-day survivors^[6].
L-Histidinol dihydrochloride (7 mg/mouse; i.p.; 4 consecutive days a week, with 5 doses at 2-h intervals; for 3 weeks) significantly inhibits tumor growth in CD8F1 breast tumor mice^[7].
L-Histidinol (100 mg/kg; i.p.; once every 2 h for 5 times; starting 2 h before Cisplatin administration) dihydrochloride reduces Cisplatin (HY-17394)-induced nephrotoxicity in rats and protects renal function^[8].
L-Histidinol (0.5%, p.o., drinking water, 3 days before Ifosfamide administration and daily thereafter) dihydrochloride attenuates Fanconi syndrome induced by Ifosfamide (HY-17419) in rats^[9].