DD-CIP2

DD-CIP2 is a DNA damage and apoptosis inducer. DD-CIP2 demonstrates effective anti-proliferative activity against multiple cancer cell. DD-CIP2 modulates the DNA damage response pathway, triggering robust DNA damage, cell cycle arrest, and apoptosis in vitro. DD-CIP2 demonstrates significant anti-tumor efficacy in vivo at well-tolerated doses, without substantial toxicity. DD-CIP2 exhibits superior cytotoxic potency against a broad panel of blood-and solid-tumor-derived cancer cell lines independent of their BRCA1/2 status. DD-CIP2 can be used for small-cell lung cancer (SCLC) and non small-cell lung cancer (NSCLC) research ^[1].

In Vivo, DD-CIP2 (20 mg/kg, i.p., once for 5 days or 28 days) achieves potent and well-tolerated anti- tumor activity with no apparent systemic toxicity in a human SCLC xenograft mice model^[1].

In Vitro, DD-CIP2 can target a broad spectrum of cancers with IC₅₀ = 12 nM in Jurkat cell, IC₅₀ = 12 nM in KARPASS422 cell, IC₅₀ = 11 nM in Raji cell, IC₅₀ = 2 nM in Daudi cell, IC₅₀ = 9.3 nM in TYK-nu cell, and IC₅₀ < 10 nM in MDA-MB-436, IC₅₀ = 0.8 nM in SU-DHL-5 cells, IC₅₀ = 4.6 nM in MOLT-4^[1]. ^[1] DD-CIP2 displays only a modest increase of PARP1 occupancy with EC50 = 42 nM^[1]. DD-CIP2 (0.1-100 nM, 24 h) induces PARP1-BRD4 interaction in HEK293T cells and reduces DNA damage in both GLC16 and NCI-H82 cell lines^[1]. DD-CIP2 (0.1-0.8 nM, 72 h) demonstrates the dependency on the PARP-170 BRD4 association in SU-DHL-5 cell^[1]. DD-CIP2 (10 μM, 24 h) stalles cell cycle progression in GLC16 cells^[1].

References:
[1]. Qiu T, et al. Design and Development of DNA Damage Chemical Inducers of Proximity (DD-CIP) for Targeted Cancer Therapy. bioRxiv [Preprint]. 2025 Nov 4:2025.11.03.686423.