IBERDOMIDE

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C25H27N3O5
Molecular Weight	449.499
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

O=C1N(CC2=C1C=CC=C2OCC3=CC=C(CN4CCOCC4)C=C3)[C@H]5CCC(=O)NC5=O

InChI

InChIKey=IXZOHGPZAQLIBH-NRFANRHFSA-N

InChI=1S/C25H27N3O5/c29-23-9-8-21(24(30)26-23)28-15-20-19(25(28)31)2-1-3-22(20)33-16-18-6-4-17(5-7-18)14-27-10-12-32-13-11-27/h1-7,21H,8-16H2,(H,26,29,30)/t21-/m0/s1

HIDE SMILES / InChI

Molecular Formula	C25H27N3O5
Molecular Weight	449.499
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

Description

CC-220 is a potent cereblon modulating agent that displays anti-proliferative, pro-apoptotic and immunomodulatory activity on sensitive and resistant multiple myeloma cell lines. CC-220 is currently under clinical investigation for systemic lupus erythematosus and multiple myeloma as a single agent, or in combination with dexamethasone in patients who may have previously been exposed to pomalidomide. Comparable to other Cereblon-binding agents, ex vivo treatment of CC-220 on B-cells, T-cells, and monocytes leads to the degradation of the hematopoietic transcription factors Ikaros (IKZF1) and Aiolos (IKZF3). followed by disruption of the multiple myeloma promoting c-Myc/IRF4 axis.

Originator

Approval Year

Targets

Targets

Primary Target	Pharmacology	Condition	Potency
Protein cereblon 10	Binding Agent 1,076

C_max

Value	Dose	Analyte	Population
3.34 ng/mL	1 mg single, oral	CC-220 plasma	Homo sapiens
2.61 ng/mL	1 mg single, oral	CC-220 plasma	Homo sapiens
3.06 ng/mL	1 mg single, oral	CC-220 plasma	Homo sapiens
3.62 ng/mL	1 mg single, oral	CC-220 plasma	Homo sapiens
2.85 ng/mL	1 mg single, oral	CC-220 plasma	Homo sapiens
0.3 ng/mL	0.1 mg single, oral	CC-220 plasma	Homo sapiens
0.7 ng/mL	0.3 mg single, oral	CC-220 plasma	Homo sapiens
2.7 ng/mL	1 mg single, oral	CC-220 plasma	Homo sapiens
4.8 ng/mL	2 mg single, oral	CC-220 plasma	Homo sapiens
10.1 ng/mL	4 mg single, oral	CC-220 plasma	Homo sapiens
17.7 ng/mL	6 mg single, oral	CC-220 plasma	Homo sapiens
2.2 ng/mL	1 mg single, oral	CC-220 plasma	Homo sapiens
2.3 ng/mL	1 mg single, oral	CC-220 plasma	Homo sapiens

AUC

Value	Dose	Analyte	Population
52.8 ng × h/mL	1 mg single, oral	CC-220 plasma	Homo sapiens
41.9 ng × h/mL	1 mg single, oral	CC-220 plasma	Homo sapiens
49.3 ng × h/mL	1 mg single, oral	CC-220 plasma	Homo sapiens
45.4 ng × h/mL	1 mg single, oral	CC-220 plasma	Homo sapiens
43.2 ng × h/mL	1 mg single, oral	CC-220 plasma	Homo sapiens
4.9 ng × h/mL	0.1 mg single, oral	CC-220 plasma	Homo sapiens
9.8 ng × h/mL	0.3 mg single, oral	CC-220 plasma	Homo sapiens
45 ng × h/mL	1 mg single, oral	CC-220 plasma	Homo sapiens
78.2 ng × h/mL	2 mg single, oral	CC-220 plasma	Homo sapiens
153.3 ng × h/mL	4 mg single, oral	CC-220 plasma	Homo sapiens
255.1 ng × h/mL	6 mg single, oral	CC-220 plasma	Homo sapiens
40.4 ng × h/mL	1 mg single, oral	CC-220 plasma	Homo sapiens
38.7 ng × h/mL	1 mg single, oral	CC-220 plasma	Homo sapiens

T_1/2

Value	Dose	Analyte	Population
17.4 h	1 mg single, oral	CC-220 plasma	Homo sapiens
14.3 h	1 mg single, oral	CC-220 plasma	Homo sapiens
17 h	1 mg single, oral	CC-220 plasma	Homo sapiens
17 h	1 mg single, oral	CC-220 plasma	Homo sapiens
15.3 h	1 mg single, oral	CC-220 plasma	Homo sapiens
11.2 h	0.1 mg single, oral	CC-220 plasma	Homo sapiens
8.8 h	0.3 mg single, oral	CC-220 plasma	Homo sapiens
13.2 h	1 mg single, oral	CC-220 plasma	Homo sapiens
13.4 h	2 mg single, oral	CC-220 plasma	Homo sapiens
12.1 h	4 mg single, oral	CC-220 plasma	Homo sapiens
17.7 h	6 mg single, oral	CC-220 plasma	Homo sapiens
11.8 h	1 mg single, oral	CC-220 plasma	Homo sapiens
13.7 h	1 mg single, oral	CC-220 plasma	Homo sapiens

F_unbound

Value	Dose	Co-administered	Analyte	Population
32%	single, unknown		CC-220 plasma	Homo sapiens

PubMed

Title	Date	PubMed
No data available in table

Patents

Sample Use Guides

In Vivo Use Guide

0.3 mg for 21 days of a 28-day cycle

Route of Administration: Oral

Substance Class	Chemical
Record UNII	8V66F27X44
Record Status	`Validated (UNII)`
Record Version

Show entries

Name

Type

Language

(3S)-3-[4-({4-[(Morpholin-4-yl)methyl]phenyl}methoxy)-1-oxo-1,3-dihydro-2H-isoindol-2-yl]piperidine-2,6-dione

Preferred Name

English

IBERDOMIDE

Official Name

English

Iberdomide [WHO-DD]

Common Name

English

2,6-PIPERIDINEDIONE, 3-(1,3-DIHYDRO-4-((4-(4-MORPHOLINYLMETHYL)PHENYL)METHOXY)-1-OXO-2H-ISOINDOL-2-YL)-, (3S)-

Systematic Name

English

(S)-3-(4-((4-(MORPHOLINOMETHYL)BENZYL)OXY)-1-OXOISOINDOLIN-2-YL)PIPERIDINE-2,6-DIONE

Systematic Name

English

Showing 1 to 5 of 8 entries

Previous1 2Next

Show entries

Classification Tree

Code System

Code

Designated

FDA ORPHAN DRUG

665718

Pharmacologic Substance

NCI_THESAURUS

C308

Showing 1 to 2 of 2 entries

Previous1Next

Show entries

Code System

Code

Type

Description

PUBCHEM

67335295

PRIMARY

NCI_THESAURUS

C129048

PRIMARY

USAN

DE-06

PRIMARY

DRUG BANK

DB12101

PRIMARY

CAS

1323403-33-3

PRIMARY

Showing 1 to 5 of 8 entries

Previous1 2Next

Show entries

Related Record

Type

Details


					HR6E2AWX74

CEREBLON

TARGET -> INHIBITOR

Comments:

CRBN ubiquitination studies in the transfected HEK293T cells resulted in the following potencies: CC-220 IC50 = 0.19 ?M; lenalidomide IC50 = 12.9 ?M; and pomalidomide IC50 = 21.6 ?M

Qualification:

IC50

Amount:

190 NANOMOLAR (average)


					HR6E2AWX74

CEREBLON

TARGET -> INHIBITOR

Comments:

Competitive CRBN binding studies, preincubation with pomalidomide at a concentration of 3 ?M resulted in approximately 50% less CRBN bound to the affinity beads, while CC-220 at a concentration of 0.1 ?M resulted in similar CRBN binding.

Interaction Type:

BINDING

Qualification:

IC50

Amount:

100 NANOMOLAR (average)