PARP1/2/TNKS1/2-IN-1

Name: PARP1/2/TNKS1/2-IN-1
Brand: MedChemExpress
SKU: HY-146336
Rating: 4.5 (0 reviews)

Cat. No.: HY-146336 Purity: 98.66%: Data Sheet
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PARP1/2/TNKS1/2-IN-1 is a potent and selective dual PARP-1/2 and TNKS1/2 inhibitor with IC₅₀ values of 0.25 nM, 1.2 nM, 13.5 nM and 4.15 nM for PARP-1, PARP-2, TNKS1 and TNKS2, respectively. PARP1/2/TNKS1/2-IN-1 suppresses Wnt/β-catenin signaling, decreases pADPr and BRCA1 expression, induces DNA damage, promotes apoptosis, and arrests the cell cycle at the G2/M phase. PARP1/2/TNKS1/2-IN-1 can be used for the study of on colorectal cancer and triple-negative breast cancer.

For research use only. We do not sell to patients.

PARP1/2/TNKS1/2-IN-1 Chemical Structure

CAS No. : 2243453-32-7

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1 mg	In-stock	Estimated Time of Arrival: December 31
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•Related Screening Libraries:

•Related Small Molecules:

•Related Proteins:

View All PARP Isoform Specific Products:

View All Isoforms

PARP PARP1 PARP2 PARP3 PARP4 TNKS1/PARP5A TNKS2/PARP5B PARP7 PARP10 PARP14 PARP15 PARP12 PARP16

View All Wnt Isoform Specific Products:

View All Isoforms

Wnt1 Wnt2 Wnt3 Wnt5 Wnt7 Wnt11

Biological Activity
Purity & Documentation
References
Customer Review

Description

IC₅₀ & Target^[1]

PARP-1

0.25 nM (IC₅₀)

PARP-2

1.2 nM (IC₅₀)

TNKS2

4.15 nM (IC₅₀)

TNKS1

13.5 nM (IC₅₀)

PARP-7

15 nM (IC₅₀)

PARP-10

140 nM (IC₅₀)

PARP-12

371 nM (IC₅₀)

PARP-14

1369 nM (IC₅₀)

Cellular Effect

Cell Line	Type	Value	Description	References
AML12	CC₅₀	117.47 μM Compound: I-9	Cytotoxicity against mouse AML12 cells assessed as reduction in cell viability incubated for 7 days by MTT assay Cytotoxicity against mouse AML12 cells assessed as reduction in cell viability incubated for 7 days by MTT assay	[PMID: 35504210]
HCT-116	IC₅₀	0.75 μM Compound: I-9	Antiproliferative activity against human HCT-116 cells assessed as inhibition of cell growth incubated for 7 days by MTT assay Antiproliferative activity against human HCT-116 cells assessed as inhibition of cell growth incubated for 7 days by MTT assay	[PMID: 35504210]
MDA-MB-231	IC₅₀	0.87 μM Compound: I-9	Antiproliferative activity against human MDA-MB-231 cells assessed as inhibition of cell growth incubated for 7 days by MTT assay Antiproliferative activity against human MDA-MB-231 cells assessed as inhibition of cell growth incubated for 7 days by MTT assay	[PMID: 35504210]
MDA-MB-468	IC₅₀	0.09 μM Compound: I-9	Antiproliferative activity against human MDA-MB-468 cells assessed as inhibition of cell growth incubated for 7 days by MTT assay Antiproliferative activity against human MDA-MB-468 cells assessed as inhibition of cell growth incubated for 7 days by MTT assay	[PMID: 35504210]

In Vitro

PARP1/2/TNKS1/2-IN-1 (compound I-9) inhibits PARP-1, PARP-2, TNKS1 and TNKS2 with IC₅₀ values of 0.25 nM, 1.2 nM, 13.5 nM and 4.15 nM, respectively; it also inhibits PARP-7, PARP-10, PARP-12 and PARP-14 with IC₅₀ values of 15.0 nM, 140.0 nM, 371.0 nM and 1369.0 nM, respectively, and shows weak or no inhibitory activity against 208 tested kinases at 1 μM^[1].
PARP1/2/TNKS1/2-IN-1 (0.01-10 μM; 7 days) inhibits MDA-MB-231, HCT116 and MDA-MB-468 cancer cell proliferation, with IC₅₀ values of 0.87 μM, 0.75 μM and 0.09 μM, respectively^[1].
PARP1/2/TNKS1/2-IN-1 shows low cytotoxicity in AML12 cells, with a CC₅₀ of 117.47 μM^[1].
PARP1/2/TNKS1/2-IN-1 (10 μM) modulates PARP- and Wnt/β-catenin-related signaling in HCT116 cells by decreasing pADPr, active β-catenin, total β-catenin, cyclin D1 and BRCA1 expression, and increasing axin2 expression^[1].
PARP1/2/TNKS1/2-IN-1 (1 μM; 72 h) reduces RAD51 foci formation and increases γH2AX nuclear foci in HCT116 cells^[1].
PARP1/2/TNKS1/2-IN-1 (1, 5 μM; 3 days) promotes apoptosis and arrests the cell cycle at the G2/M phase in HCT116 cells^[1].

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

Cell Proliferation Assay^[1]

Cell Line:	MDA-MB-231, HCT116, MDA-MB-468
Concentration:	0.01-10 μM
Incubation Time:	7 days
Result:	Inhibited MDA-MB-231, HCT116, MDA-MB-468 cell proliferation, with IC₅₀ values of 0.87 μM, 0.75 μM and 0.09 μM, respectively.

Immunofluorescence^[1]

Cell Line:	HCT116
Concentration:	1 μM
Incubation Time:	72 h
Result:	Reduced RAD51 foci formation and impaired homologous recombination repair efficiency. Increased nuclear γH2AX foci, indicating enhanced DNA double-strand damage.

Apoptosis Analysis^[1]

Cell Line:	HCT116
Concentration:	1, 5 μM
Incubation Time:	3 days
Result:	Promoted HCT116 cell apoptosis. At 5 μM, induced more apoptotic cells than 5 μM Olaparib (HY-10162) and 5 μM E7449 (HY-12418).

Cell Cycle Analysis^[1]

Cell Line:	HCT116
Concentration:	1, 5 μM
Incubation Time:	3 days
Result:	Promoted the G1/S transition and arrested the cell cycle at the G2/M phase at 1 μM and 5 μM.

Parmacokinetics

Species	Dose	Route	T_1/2	T_max	C_max	C₀	AUC_0-t	AUC_0-∞	V_z	CL	MRT_0-t	MRT_0-∞
Rat^[1]	1 mg/kg	i.v.	1.73 h	0.083 h	28.7 ng/mL	389.0 ng/mL	175.6 ng·h/mL	184.1 ng·h/mL	13571 mL/kg	5440 mL/h/kg	0.77 h	1.13 h

In Vivo

PARP1/2/TNKS1/2-IN-1 (compound I-9) (25-100 mg/kg; i.p.; once daily; for 28 days) has antitumor activity in HCT116 cell-derived xenograft mouse model^[1].
PARP1/2/TNKS1/2-IN-1 (500 mg/kg; i.p.; single dose) shows no obvious acute toxicity or intestinal toxicity in Sprague-Dawley rats^[1].

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

Animal Model:	Female BALB/c nude mice, 5-6 weeks old, 18-20 g, subcutaneously inoculated with 5 × 10⁶ HCT116 cells on the right flank^[1]
Dosage:	25, 50, 100 mg/kg
Administration:	Intraperitoneal injection (i.p.); once daily; for 28 days
Result:	Suppressed HCT116 xenograft tumor growth in a dose-dependent manner. Achieved a TGI of 31.73% at 25 mg/k. Achieved significant antitumor activity at 100 mg/kg, with a TGI of 51.74%. Reduced tumor volume and tumor weight compared with the control group. Did not cause remarkable toxicity, side effects or obvious body weight decrease during the 28-day dosing period.

Animal Model:	Sprague-Dawley rat acute toxicity and intestinal toxicity model, half male and half female^[1]
Dosage:	500 mg/kg
Administration:	Intraperitoneal injection (i.p.); single dose
Result:	Caused no rat death after a single-dose administration. Did not induce significant body weight loss from day 0 to day 7. Showed no obvious intestinal toxicity in the duodenum, jejunum, ileum and colon according to histopathological analysis.

Molecular Weight

634.66

Formula

C₃₅H₃₁FN₆O₅

CAS No.

2243453-32-7

Appearance

Solid

Color

White to light yellow

SMILES

O=C(N1CCN(C(C2=CC(CC3=NNC(C4=C3C=CC=C4)=O)=CC=C2F)=O)CC1)NC5=CC=C(C(NC6=CC=C(OC)C=C6)=O)C=C5

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

Purity & Documentation

Purity: 98.66%

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Data Sheet (276 KB) SDS (252 KB)

COA (247 KB) HNMR (112 KB) LCMS (165 KB)

Handling Instructions (2659 KB)

References

[1]. Xu Y, et al. Rational design, synthesis and biological evaluation of dual PARP-1/2 and TNKS1/2 inhibitors for cancer therapy. Eur J Med Chem. 2022 Jul 5;237:114417. [Content Brief]