2064292-12-0
Chemical Structure
A1874
- CAS No.: 2064292-12-0
- Formula:C58H62Cl3F2N9O7S
- Molecular Weight:1173.59
IUPAC Name: (2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-N-(4-((1-((S)-4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)-2-oxo-6,9,12-trioxa-3-azatetradecan-14-yl)carbamoyl)-2-methoxyphenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamide
InChIKey: IPNTVOAQOGRLQB-JJMBTQCASA-N
SMILES: ClC(C=C1)=CC=C1C2=N[C@H](C3=NN=C(C)N3C4=C2C(C)=C(C)S4)CC(NCCOCCOCCOCCNC(C5=CC(OC)=C(NC([C@H]6[C@H](C7=C(F)C(Cl)=CC=C7)[C@](C8=CC=C(Cl)C=C8F)(C#N)[C@H](CC(C)(C)C)N6)=O)C=C5)=O)=O
Biological Activity: A1874 is an orally active BRD4 PROTAC degrader with a DC50 of 32 nM. A1874 degrades BRD4 via the ubiquitin-proteasome system by recruiting the MDM2 E3 ligase, while disrupting the MDM2-p53 interaction to stabilize p53 and upregulate p21, thereby inducing cell cycle arrest and apoptosis. A1874 exhibits selectivity for wild-type p53 cells and MDM2-amplified tumors, and it can be used in research on breast cancer, colorectal cancer, melanoma, lung cancer, lymphoma, myeloid leukemia, osteosarcoma, and glioblastoma[1][2][3][4][5].
| Cat. No. | Nom du produit | Pureté | Description | Pricing | |||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
|
A1874 | 99.77% | A1874 is an orally active BRD4 PROTAC degrader with a DC50 of 32 nM. A1874 degrades BRD4 via the ubiquitin-proteasome system by recruiting the MDM2 E3 ligase, while disrupting the MDM2-p53 interaction to stabilize p53 and upregulate p21, thereby inducing cell cycle arrest and apoptosis. A1874 exhibits selectivity for wild-type p53 cells and MDM2-amplified tumors, and it can be used in research on breast cancer, colorectal cancer, melanoma, lung cancer, lymphoma, myeloid leukemia, osteosarcoma, and glioblastoma. | ||||||||||||||||||||
|
loading...
/
|
|||||||||||||||||||||||
References
- [1]. Hines J, et al. MDM2-Recruiting PROTAC Offers Superior, Synergistic Antiproliferative Activity via Simultaneous Degradation of BRD4 and Stabilization of p53. Cancer research. 2019 Jan 01;79(1):251-262. [Content Brief]
- [2]. Qin AC, et al. The therapeutic effect of the BRD4-degrading PROTAC A1874 in human colon cancer cells. Cell death & disease. 2020 Sep 25;11(9):805.
- [3]. Fatima Z, et al. MDM2 Amplification Enables Selective PROTAC Targeting of Tumor Cells. Molecular cancer therapeutics. 2026 Jun 01;25(6):948-956.
- [4]. Patel H, et al. Leveraging Carnitine-functionalized Lipid Nanocarrier based Targeted Delivery of A1874 PROTAC for Glioblastoma. Pharmaceutical research. 2026 Jul 01.
- [5]. Marvalim C, et al. Abstract P49: PROTAC A1874: A Potential Targeted Therapy for Breast Cancer[J]. Cancer Research, 2024, 84(8_Supplement): P49-P49.
