Zn-DPA-maytansinoid conjugate 1 是一种类美坦素偶联物，靶向小分子免疫检查点。Zn-DPA-maytansinoid conjugate 1 可诱导肿瘤生长持续消退，使肿瘤微环境 (TME) 恢复活力、变成“发炎热肿瘤”。
| 生物活性 | Zn-DPA-maytansinoid conjugate 1 is a small molecule-based maytansinoid conjugate targeting immune checkpoint. Zn-DPA-maytansinoid conjugate 1 induces lasting regression of tumor growth and rejuvenates tumor microenvironment (TME) to an “inflamed hot tumor”[1]. |
体外研究
(In Vitro) | Zn-DPA-maytansinoid conjugate 1 (compound 40a) (0-20 mM; 72 h) inhibits the growth of human pancreatic cancer MIA PaCa2 cells and triple-negative breast cancer HCC1806 cells and displays no effect on normal fibroblast (Detroit 551)[1].
Zn-DPA-maytansinoid conjugate 1 increases CD8+T cell infiltration significantly in the tumor mass that sensitized tumors from the intrinsic immune-suppressive TME[1].
Zn-DPA-maytansinoid conjugate 1 induces tumor inflammation-related mRNA expression such as STAT1, CXCL10, CCL5, and CCL2[1].
Zn-DPA-maytansinoid conjugate 1 leads to rejuvenation of TME with enhancement in T cell, macrophage, NK cell, chemokine, and cytokine functions[1].
Cell Viability Assay[1] | Cell Line: | Detroit 551, human pancreatic cancer MIA PaCa2 cells and triple-negative breast cancer HCC1806 cells | | Concentration: | 0-20 mM | | Incubation Time: | 72 hours | | Result: | Inhibited cancer cells with IC50s of 676 nM (MIA PaCa2) and 39 nM (HCC1806), respectively.
Showed low cytotoxicity against Detroit 551 cells (IC50>20 mM). |
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体内研究
(In Vivo) | Zn-DPA-maytansinoid conjugate 1 (compound 40a) (1-2.5 mg/kg; i.v.; twice a week for 2 weeks) effectively shrank the growth of many solid tumors, exerts antipancreatic cancer, anti-triple-negative breast cancer and anti-sorafenib-resistant HCC tumor activities[1].
| Animal Model: | Nude mice bearing MIA PaCa-2, HCC1806 or sorafenib-resistant HCC xenograft tumors, respectively[1] | | Dosage: | 1 mg/kg, 2 mg/kg, 2.5 mg/kg | | Administration: | Intravenous injection; twice (day 1 and day 4) a week for 2 weeks; measured tumor twice weekly | | Result: | Resulted a lasting regression of tumor growth. |
| Animal Model: | Male SD rats (8-week-old)[1] | | Dosage: | 1 mg/kg | | Administration: | Intravenous injection; once a week for 4 weeks (days 1, 8, 15, and 22); measured body weights daily | | Result: | Showed no effect on rats body weight. |
| Animal Model: | Pharmacokinetic study in ICR mice (6-week-old) bearing HCC1806 tumors[1] | | Dosage: | 5 mg/kg (in 10% DMA/20% Cremophor EL/70% (5% dextrose)) | | Administration: | Intravenous injection; single dose; collected blood samples at 0.003, 0.083, 0.25, 0.5, 1, 2, 4, 6, 8, and 24 h and collected tumor samples at 0.5, 2, 6, 24, 72, and 168 h | | Result: | CL (mL/min/kg)=0.9; Vss(L/kg)=0.12; AUC (0-24 h) (ng/mL·h)=105599. |
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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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