Siremadlin

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C26H24Cl2N6O4
Molecular Weight	555.413
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

COC1=NC=C(C2=NC3=C([C@@H](N(C3=O)C4=CC(Cl)=CN(C)C4=O)C5=CC=C(Cl)C=C5)N2C(C)C)C(OC)=N1

InChI

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

HIDE SMILES / InChI

Molecular Formula	C26H24Cl2N6O4
Molecular Weight	555.413
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Originator

Approval Year

Targets

Targets

Primary Target	Pharmacology	Condition	Potency
Tumour suppressor p53/oncoprotein Mdm2 6	Inhibitor 8,504		0.13 nM [IC50]

C_max

Value	Dose	Analyte	Population
118 ng/mL	12.5 mg single, oral	SIREMADLIN plasma	Homo sapiens
121 ng/mL	12.5 mg 1 times / 3 weeks multiple, oral	SIREMADLIN plasma	Homo sapiens
100 ng/mL	25 mg single, oral	SIREMADLIN plasma	Homo sapiens
126 ng/mL	25 mg 1 times / 3 weeks multiple, oral	SIREMADLIN plasma	Homo sapiens
467 ng/mL	50 mg single, oral	SIREMADLIN plasma	Homo sapiens
499.9 ng/mL	50 mg 1 times / 3 weeks multiple, oral	SIREMADLIN plasma	Homo sapiens
663.3 ng/mL	100 mg single, oral	SIREMADLIN plasma	Homo sapiens
778.9 ng/mL	100 mg 1 times / 3 weeks multiple, oral	SIREMADLIN plasma	Homo sapiens
1168.8 ng/mL	200 mg single, oral	SIREMADLIN plasma	Homo sapiens
1309.7 ng/mL	200 mg 1 times / 3 weeks multiple, oral	SIREMADLIN plasma	Homo sapiens
2258.8 ng/mL	350 mg single, oral	SIREMADLIN plasma	Homo sapiens
1533.5 ng/mL	250 mg 1 times / 3 weeks multiple, oral	SIREMADLIN plasma	Homo sapiens
2015.7 ng/mL	250 mg single, oral	SIREMADLIN plasma	Homo sapiens
2601.3 ng/mL	350 mg 1 times / 3 weeks multiple, oral	SIREMADLIN plasma	Homo sapiens
3750.4 ng/mL	400 mg single, oral	SIREMADLIN plasma	Homo sapiens
3199.1 ng/mL	400 mg 1 times / 3 weeks multiple, oral	SIREMADLIN plasma	Homo sapiens
1039.5 ng/mL	120 mg single, oral	SIREMADLIN plasma	Homo sapiens
856.9 ng/mL	120 mg 1 times / week multiple, oral	SIREMADLIN plasma	Homo sapiens
851.6 ng/mL	120 mg 1 times / 3 weeks multiple, oral	SIREMADLIN plasma	Homo sapiens
1444.3 ng/mL	150 mg single, oral	SIREMADLIN plasma	Homo sapiens
1136.3 ng/mL	150 mg 1 times / week multiple, oral	SIREMADLIN plasma	Homo sapiens
1430.5 ng/mL	150 mg 1 times / 3 weeks multiple, oral	SIREMADLIN plasma	Homo sapiens
2051.2 ng/mL	200 mg single, oral	SIREMADLIN plasma	Homo sapiens
1160 ng/mL	200 mg 1 times / week multiple, oral	SIREMADLIN plasma	Homo sapiens
1421.1 ng/mL	200 mg 1 times / 3 weeks multiple, oral	SIREMADLIN plasma	Homo sapiens

AUC

Value	Dose	Analyte	Population
1483.1 ng × h/mL	12.5 mg single, oral	SIREMADLIN plasma	Homo sapiens
1359.7 ng × h/mL	12.5 mg 1 times / 3 weeks multiple, oral	SIREMADLIN plasma	Homo sapiens
1773.6 ng × h/mL	25 mg single, oral	SIREMADLIN plasma	Homo sapiens
1879.7 ng × h/mL	25 mg 1 times / 3 weeks multiple, oral	SIREMADLIN plasma	Homo sapiens
8028.8 ng × h/mL	50 mg single, oral	SIREMADLIN plasma	Homo sapiens
7178.2 ng × h/mL	50 mg 1 times / 3 weeks multiple, oral	SIREMADLIN plasma	Homo sapiens
14287 ng × h/mL	100 mg single, oral	SIREMADLIN plasma	Homo sapiens
11675.2 ng × h/mL	100 mg 1 times / 3 weeks multiple, oral	SIREMADLIN plasma	Homo sapiens
26255.2 ng × h/mL	200 mg single, oral	SIREMADLIN plasma	Homo sapiens
20070.6 ng × h/mL	200 mg 1 times / 3 weeks multiple, oral	SIREMADLIN plasma	Homo sapiens
55102.9 ng × h/mL	350 mg single, oral	SIREMADLIN plasma	Homo sapiens
22887 ng × h/mL	250 mg 1 times / 3 weeks multiple, oral	SIREMADLIN plasma	Homo sapiens
41422.3 ng × h/mL	250 mg single, oral	SIREMADLIN plasma	Homo sapiens
37768.7 ng × h/mL	350 mg 1 times / 3 weeks multiple, oral	SIREMADLIN plasma	Homo sapiens
81662.7 ng × h/mL	400 mg single, oral	SIREMADLIN plasma	Homo sapiens
48124.6 ng × h/mL	400 mg 1 times / 3 weeks multiple, oral	SIREMADLIN plasma	Homo sapiens
18481.7 ng × h/mL	120 mg single, oral	SIREMADLIN plasma	Homo sapiens
5270 ng × h/mL	120 mg 1 times / week multiple, oral	SIREMADLIN plasma	Homo sapiens
11864.2 ng × h/mL	120 mg 1 times / 3 weeks multiple, oral	SIREMADLIN plasma	Homo sapiens
23727.1 ng × h/mL	150 mg single, oral	SIREMADLIN plasma	Homo sapiens
6323.4 ng × h/mL	150 mg 1 times / week multiple, oral	SIREMADLIN plasma	Homo sapiens
17921 ng × h/mL	150 mg 1 times / 3 weeks multiple, oral	SIREMADLIN plasma	Homo sapiens
19303 ng × h/mL	200 mg single, oral	SIREMADLIN plasma	Homo sapiens
4886.2 ng × h/mL	200 mg 1 times / week multiple, oral	SIREMADLIN plasma	Homo sapiens
14701.4 ng × h/mL	200 mg 1 times / 3 weeks multiple, oral	SIREMADLIN plasma	Homo sapiens

T_1/2

Value	Dose	Analyte	Population
7.2 h	12.5 mg single, oral	SIREMADLIN plasma	Homo sapiens
8.7 h	12.5 mg 1 times / 3 weeks multiple, oral	SIREMADLIN plasma	Homo sapiens
31.1 h	25 mg single, oral	SIREMADLIN plasma	Homo sapiens
22.6 h	25 mg 1 times / 3 weeks multiple, oral	SIREMADLIN plasma	Homo sapiens
11 h	50 mg single, oral	SIREMADLIN plasma	Homo sapiens
15 h	50 mg 1 times / 3 weeks multiple, oral	SIREMADLIN plasma	Homo sapiens
17.1 h	100 mg single, oral	SIREMADLIN plasma	Homo sapiens
19.9 h	100 mg 1 times / 3 weeks multiple, oral	SIREMADLIN plasma	Homo sapiens
18.5 h	200 mg single, oral	SIREMADLIN plasma	Homo sapiens
23.1 h	200 mg 1 times / 3 weeks multiple, oral	SIREMADLIN plasma	Homo sapiens
14 h	350 mg single, oral	SIREMADLIN plasma	Homo sapiens
20.3 h	250 mg 1 times / 3 weeks multiple, oral	SIREMADLIN plasma	Homo sapiens
15.5 h	250 mg single, oral	SIREMADLIN plasma	Homo sapiens
22.8 h	350 mg 1 times / 3 weeks multiple, oral	SIREMADLIN plasma	Homo sapiens
18.8 h	400 mg single, oral	SIREMADLIN plasma	Homo sapiens
40.1 h	400 mg 1 times / 3 weeks multiple, oral	SIREMADLIN plasma	Homo sapiens
12.4 h	120 mg single, oral	SIREMADLIN plasma	Homo sapiens
5.5 h	120 mg 1 times / week multiple, oral	SIREMADLIN plasma	Homo sapiens
13.9 h	120 mg 1 times / 3 weeks multiple, oral	SIREMADLIN plasma	Homo sapiens
13.1 h	150 mg single, oral	SIREMADLIN plasma	Homo sapiens
13.4 h	150 mg 1 times / 3 weeks multiple, oral	SIREMADLIN plasma	Homo sapiens
6.4 h	200 mg single, oral	SIREMADLIN plasma	Homo sapiens
6.8 h	200 mg 1 times / 3 weeks multiple, oral	SIREMADLIN plasma	Homo sapiens

PubMed

Show entries

Title	Date	PubMed
Discovery of a novel class of highly potent inhibitors of the p53-MDM2 interaction by structure-based design starting from a conformational argument.	2016 Oct 1	27542305

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Patents

Substance Class	Chemical
Record UNII	0282IF4JC8
Record Status	`Validated (UNII)`
Record Version

Show entries

Name

Type

Language

Siremadlin

Official Name

English

Pyrrolo[3,4-d]imidazol-4(1H)-one, 5-(5-chloro-1,2-dihydro-1-methyl-2-oxo-3-pyridinyl)-6-(4-chlorophenyl)-2-(2,4-dimethoxy-5-pyrimidinyl)-5,6-dihydro-1-(1-methylethyl)-, (6S)-

Preferred Name

English

NVP-HDM 201

Code

English

HDM201

Code

English

SIREMADLIN [USAN]

Common Name

English

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Code System

Code

Type

Description

FDA UNII

0282IF4JC8

PRIMARY

INN

10869

PRIMARY

NCI_THESAURUS

C116325

PRIMARY

USAN

KL-119

PRIMARY

CAS

1448867-41-1

PRIMARY

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Amount:

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SMILES

InChI

Originator

Approval Year

Targets

Cmax

AUC

T1/2

PubMed

Patents

C_max

T_1/2