1. Apoptosis
  2. Apoptosis
  3. 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.

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DD-CIP2

DD-CIP2 Chemical Structure

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Description

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 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].

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

Western Blot Analysis[1]

Cell Line: HEK293T cells
Concentration: 0.1, 1, 10 and 100 nM
Incubation Time: 24 h
Result: Elevated levels of γH2AX and cleaved PARP1 in both GLC16 and NCI-H82 cell.
Increased the phosphorylation of RPA32 at Ser4/Ser8 in both GLC16 and NCI-H82 cell.

Cell Cycle Analysis[1]

Cell Line: GLC16 cells
Concentration: 10 μM
Incubation Time: 24 h
Result: Provoked a dose-dependent accumulation of 199 cells in the G2/M phase.
Parmacokinetics
Species Dose Route T1/2 Tmax Cmax
Mice[1] 10 mg/kg i.p. 2.75 h 1 h 3.90 μM
Mice[1] 3 mg/kg i.v. 3 h 0.08 h 7.66 μM
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].

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

Animal Model: GLC16 cells (2 × 106, s.c.) induced NU-Foxn1nu mice (8 weeks)[1]
Dosage: 20 mg/kg
Administration: i.p., once for 5 days
Result: Induced a dose-dependent increase in γH2AX and cleaved PARP1, confirming target engagement.
Was well tolerated at doses up to 20 mg/kg, with no significant body weight loss.
Animal Model: GLC16 cells (2 × 106, s.c.) induced NU-Foxn1nu mice (8 weeks)[1]
Dosage: 20 mg/kg
Administration: i.p., once for 28 days
Result: Showed strong tumor regression as early as day 3, with 210 durable suppression maintained throughout the experiment period.
Detected no obvious toxicity as indicated by steady body weight.
Molecular Weight

985.57

Formula

C52H54ClFN10O5S

SMILES

FC1=CC=C(CC2=NNC(C3=CC=CC=C32)=O)C=C1C(N(CC4)CCN4C(C(CC5)CCC65CCN(C(CNC(C[C@H]7C8=NN=C(C)N8C(SC(C)=C9C)=C9C(C%10=CC=C(Cl)C=C%10)=N7)=O)=O)CC6)=O)=O

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Room temperature in continental US; may vary elsewhere.

Storage

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

Purity & Documentation
References
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  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

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DD-CIP2
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HY-179585
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