Siremadlin - ≥99% , Tumour suppressor p53/oncoprotein Mdm2 inhibitor, CAS No.1448867-41-1, Tumour suppressor p53/oncoprotein Mdm2 inhibitor

CAS: 1448867-41-1 Cat. No.: H414082 Molecular Weight: 555.41

GRADE & PURITY ≥99%

Synonyms

HY-18658 | WHO 10869 | (Benzyloxycarbonyl-methyl-amino)-acetic acid | (4~{S})-5-(5-chloranyl-1-methyl-2-oxidanylidene-pyridin-3-yl)-4-(4-chlorophenyl)-2-(2,4-dimethoxypyrimidin-5-yl)-3-propan-2-yl-4~{H}-pyrrolo[3,4-d]imidazol-6-one | NVP-HDM201; HDM201 |

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

Overview

Information

HDM201 (Siremadlin) HDM201 (Siremadlin, NVP-HDM201) is a novel, highly potent and selective inhibitor of the p53-Mdm2 interaction with affinity constant for Mdm2 in the picomolar range and a selectivity ratio greater than 10000-fold vs Mdm4.

Targets

p53/MDM2 interaction

In vitro

HDM201 binds to the p53 binding-site of the Mdm2 protein, disrupting the interaction of the two proteins and leading to the activation of the p53 pathway. It induces robust p53-dependent cell cycle arrest and apoptosis in human p53 wild-type tumor cells. HDM201 exhibits highly selectivity across a panel of cancer cell lines.

In vivo

HDM201 displays desirable pharmacokinetic and pharmacodynamic profiles in animals together with excellent oral bioavailability. Application of the compound using various dosing schedules triggers rapid and sustained activation of p53-dependent pharmacodynamic biomarkers resulting in tumor regression in multiple xenografted models of p53 wild-type human cancers.

Specifications

Synonyms

HY-18658 | WHO 10869 | (Benzyloxycarbonyl-methyl-amino)-acetic acid | (4~{S})-5-(5-chloranyl-1-methyl-2-oxidanylidene-pyridin-3-yl)-4-(4-chlorophenyl)-2-(2, 4-dimethoxypyrimidin-5-yl)-3-propan-2-yl-4~{H}-pyrrolo[3, 4-d]imidazol-6-one | NVP-HDM201; HDM201 |

Specifications & Purity

≥99%

Biochemical and Physiological Mechanisms

HDM201 (Siremadlin, NVP-HDM201) is a novel, highly potent and selective inhibitor of the p53-Mdm2 interaction with affinity constant for Mdm2 in the picomolar range and a selectivity ratio greater than 10000-fold vs Mdm4.

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

This product requires cold chain shipping. Ground and other economy services are not available.

Action Type

INHIBITOR

Mechanism of action

Tumour suppressor p53/oncoprotein Mdm2 inhibitor

Purity

≥99%

Product Properties

• ALogP: 3.6

Names and Identifiers

• Canonical Smiles: CC(C)N1C2=C(C(=O)N(C2C3=CC=C(C=C3)Cl)C4=CC(=CN(C4=O)C)Cl)N=C1C5=CN=C(N=C5OC)OC
• IUPAC Name: (4S)-5-(5-chloro-1-methyl-2-oxopyridin-3-yl)-4-(4-chlorophenyl)-2-(2,4-dimethoxypyrimidin-5-yl)-3-propan-2-yl-4H-pyrrolo[3,4-d]imidazol-6-one
• InChIKey: AGBSXNCBIWWLHD-FQEVSTJZSA-N
• INCHI: 1S/C26H24Cl2N6O4/c1-13(2)33-21-19(30-22(33)17-11-29-26(38-5)31-23(17)37-4)25(36)34(18-10-16(28)12-32(3)24(18)35)20(21)14-6-8-15(27)9-7-14/h6-13,20H,1-5H3/t20-/m0/s1
• Isomeric SMILES: CC(C)N1C2=C(C(=O)N([C@H]2C3=CC=C(C=C3)Cl)C4=CC(=CN(C4=O)C)Cl)N=C1C5=CN=C(N=C5OC)OC
• Molecular Weight: 555.41
• Reaxy-Rn: 23820235
• Reaxys-RN_link_address: https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=23820235&ln=

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organic acids and derivatives
    • Class Carboxylic acids and derivatives
      • Subclass Carboxylic acid derivatives
        • Level5 Carboxylic acid amides
          • Level6 2-heteroaryl carboxamides

• Kingdom: Organic compounds
• Superclass: Organic acids and derivatives
• Class: Carboxylic acids and derivatives
• Subclass: Carboxylic acid derivatives
• Intermediate Tree Nodes: Carboxylic acid amides
• Direct Parent: 2-heteroaryl carboxamides
• Alternative Parents: Alkyl aryl ethers Chlorobenzenes Dihydropyridines Pyridinones N-substituted imidazoles Aryl chlorides Pyrimidines and pyrimidine derivatives Heteroaromatic compounds Tertiary carboxylic acid amides Vinylogous amides Lactams Azacyclic compounds Organonitrogen compounds Organochlorides Organic oxides Hydrocarbon derivatives
• Molecular Framework: Aromatic heteropolycyclic compounds
• Substituents: 2-heteroaryl carboxamide - Alkyl aryl ether - Halobenzene - Dihydropyridine - Pyridinone - Chlorobenzene - N-substituted imidazole - Hydropyridine - Aryl chloride - Aryl halide - Pyridine - Pyrimidine - Monocyclic benzene moiety - Benzenoid - Tertiary carboxylic acid amide - Imidazole - Vinylogous amide - Heteroaromatic compound - Azole - Lactam - Azacycle - Organoheterocyclic compound - Ether - Organic oxygen compound - Organooxygen compound - Organic nitrogen compound - Hydrocarbon derivative - Organic oxide - Organonitrogen compound - Organochloride - Organohalogen compound - Aromatic heteropolycyclic compound
• Description: This compound belongs to the class of organic compounds known as 2-heteroaryl carboxamides. These are compounds containing a heteroaromatic ring that carries a carboxamide group.
• External Descriptors: Not available

Data sources

1. Djoumbou Feunang Y, Eisner R, Knox C, Chepelev L, Hastings J, Owen G, Fahy E, Steinbeck C, Subramanian S, Bolton E, Greiner R, and Wishart DS. ClassyFire: Automated Chemical Classification With A Comprehensive, Computable Taxonomy. Journal of Cheminformatics, 2016, 8:61.

DOI: 10.1186/s13321-016-0174-y

Associated Targets(Human)

MDM2 Tchem E3 ubiquitin-protein ligase Mdm2 (2 Activities)

Discover Target: MDM2

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

MDM2 Tchem p53-binding protein Mdm-2 (4545 Activities)

Discover Target: MDM2

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

MDM4 Tchem Protein Mdm4 (729 Activities)

Discover Target: MDM4

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

Associated Targets(non-human)

rep Replicase polyprotein 1ab (378 Activities)

Discover Target: rep

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

Mechanisms of Action

Chemical and Physical Properties

• Solubility: Solubility (25°C) In vitro DMSO: 100 mg/mL (180.04 mM); Ethanol: 3 mg/mL (5.4 mM); Water: Insoluble
• Molecular Weight: 555.400 g/mol
• XLogP3: 3.600
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 7
• Rotatable Bond Count: 6
• Exact Mass: 554.124 Da
• Monoisotopic Mass: 554.124 Da
• Topological Polar Surface Area: 103.000 Ų
• Heavy Atom Count: 38
• Formal Charge: 0
• Complexity: 987.000
• Isotope Atom Count: 0
• Defined Atom Stereocenter Count: 1
• Undefined Atom Stereocenter Count: 0
• Defined Bond Stereocenter Count: 0
• Undefined Bond Stereocenter Count: 0
• The total count of all stereochemical bonds: 0
• Covalently-Bonded Unit Count: 1

References

1. Shixin Duan, Jun Wang, Xinyi Lou, Dongxin Chen, Peiyunfeng Shi, Hongchao Jiang, Zhiming Wang, Wen Li, Feng Qian.  (2023)  A novel anti-IL-33 antibody recognizes an epitope FVLHN of IL-33 and has a therapeutic effect on inflammatory diseases.  INTERNATIONAL IMMUNOPHARMACOLOGY,      [PMID:37423158] [10.1016/j.intimp.2023.110578]