VIP236 

VIP236 is a small-molecule drug conjugate targeting αvβ3 integrin. VIP236 achieves tumor homing via specific binding to αvβ3 integrin and delivers its payload to the tumor microenvironment. The linker of VIP236 is cleavable by neutrophil elastase, which is highly expressed in the tumor microenvironment, to release the payload 7-ethylcamptothecin. This payload induces DNA damage by inhibiting topoisomerase 1, thereby exerting anti-tumor effects. VIP236 exhibits excellent plasma stability and tumor targeting property, with a tumor/plasma payload ratio 10-fold higher than that of the single administration. It effectively induces tumor regression, reduces metastasis formation, and shows good tolerance in mouse models. VIP236 has been used in studies related to non-small cell lung cancer, clear cell renal cell carcinoma, colon cancer, triple-negative breast cancer, small cell lung cancer, and metastatic solid tumors^[1][2][3][4].

VIP236 (5 mg/mL; 79 days stored at 4 °C) exhibits high hydrolytic stability when stored in pH 7.4 PBS buffer, with no observable degradation^[1].
VIP236 (over 24 h incubated at 37 °C) is highly stable in rat plasma, with no observable degradation^[1].
VIP236 (1 μM; 4 h incubated at 37 °C) is highly stable in mouse, rat, dog, and human hepatocytes, with ~80% of the parent compound remaining after incubation^[1].
VIP236 (0-50 μM; up to 12 min) is efficiently cleaved by both human and mouse NE, with similar K_m values between the two enzymes; cleavage follows Michaelis-Menten kinetics with K_m values of 9.4 μM, 9.6 μM, 15.9 μM, 8.9 μM and k_cat values of 593 1/min, 691 1/min, 94 1/min, 80 1/min at the tested enzyme concentrations^[1].
VIP236 (72 h continuous exposure) exhibits NE-dependent cytotoxicity in NCI-H292 and LoVo cancer cell lines, with IC₅₀ values decreasing 117-fold and 33-fold, respectively, when 20 nM NE is present during exposure^[1].
VIP236 (1×10^-5-1×10^-13 M; 72 h) exhibits NE-dependent antiproliferative activity in 786-O, HT29, LoVo, SW480, NCI-H292, NCI-H69, and 4T1 cells, with single-digit nanomolar IC₅₀ values in most cell lines in the presence of 10 nM NE and weak activity in the absence of NE^[2].
VIP236 (1×10^-13-1×10^-5 M; 72 h) exhibits weak antiproliferative activity in 786-O, HT29, LoVo, SW480, NCI-H292, NCI-H69, and 4T1 cells without NE, but shows potent, VIP126-matched activity with single-digit nanomolar IC₅₀ values (except for 4T1 cells) when co-incubated with 10 nM NE^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

VIP236 (1-20 mg/kg; i.v.; day 1 (0 h pretreatment) and day 2 (24 h pretreatment)) induces time- and dose-dependent DNA damage in SNU16 xenograft tumors, with the 20 mg/kg dose producing 68-79% γH2AX-positive cells 24-48 h post-treatment^[1].
VIP236 (40-60 mg/kg; i.v.; 2 days on/5 days off for 4 weeks, once weekly for 4 weeks) inhibits orthotopic tumor growth and reduces micrometastases in the MA15191 metastatic TNBC PDX model, with the 40 mg/kg 2 days on/5 days off regimen achieving a 17% T/C ratio^[1].
VIP236 (36 mg/kg; i.v.; 3 days on/4 days off) induces marked antitumor efficacy in 786-O RCC xenografts, with a T/C ratio of 0.19 and no evidence of significant toxicity^[2].
VIP236 (40 mg/kg; i.v.; 3 days on/4 days off) induces marked antitumor efficacy in NCI-H69 SCLC xenografts, with a T/C ratio of 0.06 and 100% partial responses, and is more efficacious than cisplatin and topotecan while maintaining good tolerability^[2].
VIP236 (36 mg/kg; i.v.; 3 days on/4 days off) induces significant renal cell carcinoma growth inhibition in mice, with a T/C ratio of 0.19 and partial or stable disease responses in all treated animals^[3].
VIP236 (40 mg/kg; i.v.; 3 days on/4 days off) induces marked small cell lung cancer growth inhibition in all treated mice, with a T/C ratio of 0.06 and superior efficacy to cisplatin and topotecan^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

1515.55

C₇₂H₈₄N₁₂Na₂O₂₀S

2418533-90-9

O=C(O[Na])C[C@@H](NC(NC1=CC=C(NC(NCCOCCOCCOCCC(N[C@H](C(N2[C@H](C(N[C@@H](C(C)C)C(O[C@@](C(OC3)=O)(CC)C4=C3C(N(CC5=C(CC)C(C=CC=C6)=C6N=C57)C7=C4)=O)=O)=O)CCC2)=O)CC(O[Na])=O)=O)=O)C=C1)=O)C8=CC=CC(NS(C9=CC=CC(NC(NCCC)=O)=C9)(=O)=O)=C8

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Lerchen HG, et al. Discovery of VIP236, an αvβ3-Targeted Small-Molecule-Drug Conjugate with Neutrophil Elastase-Mediated Activation of 7-Ethyl Camptothecin Payload for Treatment of Solid Tumors. Cancers (Basel). 2023;15(17):4381. Published 2023 Sep 1.  [Content Brief]

  [2]. Lerchen HG, et al. A Small Molecule-Drug Conjugate (SMDC) Consisting of a Modified Camptothecin Payload Linked to an α_Vß₃ Binder for the Treatment of Multiple Cancer Types. Cancers (Basel). 2022;14(2):391. Published 2022 Jan 13.  [Content Brief]

  [3]. Yang H, et al. Identification of an αvβ3-targeting bicyclic peptide with atypical norArg-Gly-Asp sequence. Commun Chem. 2026;9(1):83. Published 2026 Jan 12.  [Content Brief]