ChemicalBook CAS DataBase List 459789-75-4

459789-75-4

Name	5-(2,4-dichlorophenyl)-1-(4-methylphenyl)-3a,6a-dihydrosprio[1H-furo[3,4-c]pyrrole-3,2'-(1'H)-indene]-1',3',4,6(2'H,3H,5H)-tetrone
CAS	459789-75-4
Molecular Formula	C27H17Cl2NO5
Molecular Weight	506.33
MOL File	459789-75-4.mol

Chemical Properties

Boiling point	782.1±60.0 °C(Predicted)
density	1.56±0.1 g/cm3(Predicted)
solubility	DMSO: 2 mg/mL, clear
form	Solid
pka	-2.53±0.40(Predicted)
color	White to off-white

Hazard Information

Uses

ML-T7 is a potent Tim-3 inhibitor. ML-T7 blocks Tim-3 interactions with PtdSer and CEACAM1. ML-T7 not only enhances the antitumor activity of adoptive transfer therapy with cytotoxic T lymphocytes (CTLs) and CAR T cells but also increases the effector function of T cell. ML-T7 promotes NK cells’ killing activity against tumor cells and DC antigen-presenting capacity. ML-T7 directly exerts antitumor efficacy in preclinical tumor models either alone or in combination with Nivolumab (HY-P9903A). ML-T7 can be used for tumor immunotherapy research[1].

in vivo

ML-T7 (10-50 mg/kg; Intraperitoneal injection; every 2 days, 10 times) inhibits the growth of tumor and prolongs survival of HCC mice, without adverse effects on mice body weight^[1].
ML-T7 (20 mg/kg; Intraperitoneal injection; every 2 days, 10 times) synergizes with Nivolumab (HY-P9903A) to improve the antitumor efficacy of Nivolumab (HY-P9903A) antibodies, and effectively improves HCC mice survival^[1].
ML-T7 (50 mg/kg, Intraperitoneal injection; every 2 days for 3 weeks)shows a good safety profile in mice^[1].

Animal Model:	10-week-old mice with spontaneous orthotopic HCC^[1]
Dosage:	10-50 mg/kg
Administration:	Intraperitoneal injection (i.p.), every 2 days, 10 times
Result:	Increased CD8⁺ T cells in both tumor and spleen. Inhibited T cell exhaustion. Promoted the function of CTLs, NK cells, and DCs.

Animal Model:	10-week-old mice with orthotopic Akt/c-Myc HCC^[1]
Dosage:	20 mg/kg
Administration:	Intraperitoneal injection (i.p.), every 2 days, 10 times
Result:	Indicated stronger antituomr activity when treated with ML-T7 and Nivolumab (HY-P9903A). Rejuvenated NK cells by the combination therapy. Inhibited the accumulation of MDSCs and Tregs.

References

[1] Ma S, et al. Identification of a small-molecule Tim-3 inhibitor to potentiate T cell-mediated antitumor immunotherapy in preclinical mouse models. Sci Transl Med. 2023 Nov 15;15(722):eadg6752. DOI:10.1126/scitranslmed.adg6752

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