Lenalidomide

Summary

Lenalidomide (CHEMBL848) is an approved small-molecule angiogenesis inhibitor (ATC L04AX04) targeting CRBN; indicated across 92 conditions including mantle cell lymphoma and immune system disorder; with CIViC clinical evidence for 1 variant-indication association (e.g. CRBN Mutation in multiple myeloma).

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: L04AX04
• Targets: 1 (CRBN)
• Indications: 92 conditions
• Clinical trials: 1,003
• Precision-oncology evidence (CIViC): 1 variant–indication association
• Chemistry: 259.26 Da · C13H13N3O3

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL848
Name	Lenalidomide
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	216326
ChEBI	CHEBI:63791
ATC	L04AX04
Molecular formula	C13H13N3O3
Molecular weight	259.26
InChIKey	GOTYRUGSSMKFNF-UHFFFAOYSA-N

SMILES: C1CC(=O)NC(=O)C1N2CC3=C(C2=O)C=CC=C3N

IUPAC name: 3-(7-amino-3-oxo-1H-isoindol-2-yl)piperidine-2,6-dione

ChEBI definition: A dicarboximide that consists of 1-oxoisoindoline bearing an amino substituent at position 4 and a 2,6-dioxopiperidin-3-yl group at position 2. Inhibits the secretion of TNF-α.

Pharmacological roles (ChEBI): angiogenesis inhibitor, antineoplastic agent, immunomodulator.

Also known as: CC-5013, CDC-501, Lenalidomida, Lenalidomide, Lenalidomide accord, Lenalidomide mylan, NSC-747972, Revlimid, SYP-1512, LENALIDOMIDE, lenalidomide, SID124893328

Parent form; salt/anhydrous children: CHEMBL6068337

Patent coverage: 1,924 distinct patent families (5,256 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 5,087 (97%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
CRBN	cereblon	Binding	5.82	0.2%	Q96SW2

Broader ChEMBL bioactivity targets: 8 (assay-derived). Sample: Bromodomain-containing protein 4, Tumor necrosis factor, Interleukin-1 beta, Protein cereblon, Cereblon/Ikaros, Protein cereblon/Zinc finger protein Aiolos, Protein cereblon/DNA damage-binding protein 1, Zinc finger protein Aiolos.

Bioactivity

ChEMBL activities: 26 potent at pChembl ≥ 5 of 29 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
IKZF3	7.3	EC50	50	nM	CHEMBL_ACT_29220692
CRBN	7.24	Kd	57	nM	CHEMBL_ACT_29075684
IKZF1	7.17	EC50	67	nM	CHEMBL_ACT_18565672
IKZF3	7.16	EC50	70	nM	CHEMBL_ACT_25673169
CRBN	7.09	IC50	81	nM	CHEMBL_ACT_29075710
CRBN	7.06	EC50	87	nM	CHEMBL_ACT_18565669
CRBN	7.05	IC50	88.99	nM	CHEMBL_ACT_25927541
DDB1	6.96	IC50	110	nM	CHEMBL_ACT_29220595
DDB1	6.77	Kd	170	nM	CHEMBL_ACT_25690971
CRBN	6.75	Kd	178	nM	CHEMBL_ACT_25848528
TNF	6.66	IC50	220	nM	CHEMBL_ACT_26678819
DDB1	6.54	IC50	286	nM	CHEMBL_ACT_24375640
CRBN	6.41	IC50	390	nM	CHEMBL_ACT_25083015
IL1B	6.41	IC50	390	nM	CHEMBL_ACT_26678804
CRBN	6.16	IC50	700	nM	CHEMBL_ACT_29075650
CRBN	6.1	Ki	800	nM	CHEMBL_ACT_26016803
DDB1	5.99	IC50	1020	nM	CHEMBL_ACT_25673121
CRBN	5.83	Ki	1490	nM	CHEMBL_ACT_20663269
CRBN	5.83	Ki	1490	nM	CHEMBL_ACT_28873508
CRBN	5.82	IC50	1500	nM	CHEMBL_ACT_18565677
CRBN	5.77	IC50	1710	nM	CHEMBL_ACT_29103058
CRBN	5.7	IC50	1980	nM	CHEMBL_ACT_29105156
CRBN	5.44	IC50	3600	nM	CHEMBL_ACT_25472084
BRD4	5.29	IC50	5190	nM	CHEMBL_ACT_20663263
CRBN	5.29	IC50	5190	nM	CHEMBL_ACT_28873505
CRBN	5.19	Ki	6400	nM	CHEMBL_ACT_25665466

Target pathways

Aggregated over 1 target gene(s): CRBN.

Top Reactome pathways

1 total, by targets touching each:

Pathway	Targets	Genes
Potential therapeutics for SARS	1	CRBN

Dominant GO biological processes

GO term	Targets
protein ubiquitination	1
positive regulation of Wnt signaling pathway	1
negative regulation of protein-containing complex assembly	1
positive regulation of protein-containing complex assembly	1
negative regulation of monoatomic ion transmembrane transport	1
locomotory exploration behavior	1
proteasome-mediated ubiquitin-dependent protein catabolic process	1
limb development	1

Indications & clinical

Indications

92 indications (6 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
mantle cell lymphoma	4	MONDO:0018876	EFO:1001469
immune system disorder	4	MONDO:0005046	EFO:0000540
myelodysplastic syndrome	4	MONDO:0018881	EFO:0000198
plasma cell myeloma	4	MONDO:0009693	EFO:0001378
anemia	4	MONDO:0002280	EFO:0004272
B-cell chronic lymphocytic leukemia	3	MONDO:0004948	EFO:0000095
MALT lymphoma	3	MONDO:0007650	EFO:0000191
acute myeloid leukemia	3	MONDO:0018874	EFO:0000222
lymphoma	3	MONDO:0005062	EFO:0000574
melanoma	3	MONDO:0005105	EFO:0000756
non-Hodgkin lymphoma	3	MONDO:0018908	EFO:0005952
diffuse large B-cell lymphoma	3	MONDO:0018905	EFO:0000403
neoplasm of mature B-cells	3	MONDO:0004949	EFO:0000096
smoldering plasma cell myeloma	3	MONDO:0005235	EFO:0003073
plasmacytoma	3	MONDO:0005615	EFO:0006738
marginal zone lymphoma	3	MONDO:0017604	EFO:1000630
Epstein-Barr virus infection	3	MONDO:0005111	EFO:0000769
follicular lymphoma	3	MONDO:0018906	MONDO:0018906
hereditary amyloidosis	3	MONDO:0018634	MONDO:0019438
plasma cell neoplasm	3	MONDO:0004959	EFO:0000200
amyloidosis	3	MONDO:0019065	EFO:1001875
hepatocellular carcinoma	2	MONDO:0007256	EFO:0000182
Hodgkins lymphoma	2	MONDO:0004952	EFO:0000183
urinary bladder neoplasm	2	MONDO:0004987	EFO:0000294
leukemia	2	MONDO:0005059	EFO:0000565
HIV infectious disease	2	MONDO:0005109	EFO:0000764
T-cell acute lymphoblastic leukemia	2	MONDO:0004963	EFO:0000209
primary myelofibrosis	2	MONDO:0009692	EFO:0002430
non-small cell lung carcinoma	2	MONDO:0005233	EFO:0003060
exocrine pancreatic carcinoma	2	MONDO:0005192	EFO:0002618
thyroid tumor	2	MONDO:0015074	EFO:0003841
peripheral T-cell lymphoma, not otherwise specified	2	MONDO:0004964	EFO:0000211
autism	2	MONDO:0005260	EFO:0003758
metastatic prostate carcinoma	2	MONDO:0004956	EFO:0000196
acute lymphoblastic leukemia	2	MONDO:0004967	EFO:0000220
Crohn disease	2	MONDO:0005011	EFO:0000384
essential thrombocythemia	2	MONDO:0005029	EFO:0000479
prostate adenocarcinoma	2	MONDO:0005082	EFO:0000673
squamous cell carcinoma	2	MONDO:0005096	EFO:0000707
acquired polycythemia vera	2	MONDO:0009891	EFO:0002429
primary cutaneous T-cell non-Hodgkin lymphoma	2	MONDO:0000607	EFO:0002913
plasma cell leukemia	2	MONDO:0018689	EFO:0006475
POEMS syndrome	2	MONDO:0017364	EFO:1001115
gliosarcoma	2	MONDO:0016681	EFO:1001465
chronic myelomonocytic leukemia	2	MONDO:0020311	EFO:1001779
hematologic disorder	2	MONDO:0005570	HP:0001871
Waldenstrom macroglobulinemia	2	MONDO:0100280	EFO:0009441
thyroid gland carcinoma	2	MONDO:0015075	EFO:0002892
colorectal neoplasm	2	MONDO:0005335	EFO:0004142
complex regional pain syndrome	2	MONDO:0019369	EFO:1001998
prolymphocytic leukemia	2	MONDO:0001023	MONDO:0001023
kidney cancer	2	MONDO:0002367	MONDO:0002367
radiculopathy	2	MONDO:0002959	MONDO:0002959
graft versus host disease	2	MONDO:0013730	MONDO:0013730
T-cell non-Hodgkin lymphoma	2	MONDO:0015760	MONDO:0015760
hematopoietic and lymphoid system neoplasm	2	MONDO:0002334	MONDO:0044881
glioma	2	MONDO:0021042	MONDO:0100342
sinus histiocytosis with massive lymphadenopathy	2	MONDO:0006412	MONDO:0006412
mature T-cell and NK-cell non-Hodgkin lymphoma	2	MONDO:0000430	MONDO:0000430
lymphoid leukemia	2	MONDO:0005402	EFO:0004289
neoplasm	1	MONDO:0005070	EFO:0000616
Kaposi’s sarcoma	1	MONDO:0005055	EFO:0000558
Burkitt lymphoma	1	MONDO:0007243	EFO:0000309
neuroblastoma	1	MONDO:0005072	EFO:0000621
renal cell carcinoma	1	MONDO:0005086	EFO:0000681
anaplastic astrocytoma	1	MONDO:0016684	EFO:0002499
chronic myeloid leukemia	1	MONDO:0011996	EFO:0000339
diffuse intrinsic pontine glioma	1	MONDO:0006033	EFO:1000026
central nervous system neoplasm	1	MONDO:0006130	EFO:1000158
rectal cancer	1	MONDO:0006519	EFO:1000657
peritoneal neoplasm	1	MONDO:0006901	MONDO:0002087
fallopian tube neoplasm	1	MONDO:0021092	MONDO:0002158
ovarian cancer	1	MONDO:0008170	MONDO:0008170
colonic neoplasm	1	MONDO:0005401	MONDO:0021063
B-cell non-Hodgkin lymphoma	1	MONDO:0015759	EFO:1001938
urethra neoplasm	1	MONDO:0021239	EFO:0003846
primary effusion lymphoma	1	MONDO:0018842	EFO:1000491
pancreatic ductal adenocarcinoma	1	MONDO:0005184	MONDO:0005184

14 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 1,003.

Phase distribution

Phase	Trials
PHASE2	455
PHASE1	179
PHASE1/PHASE2	165
PHASE3	142
Not specified	30
PHASE4	14
PHASE2/PHASE3	10
EARLY_PHASE1	8

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03829371	PHASE4	ACTIVE_NOT_RECRUITING	STUDY COMPARING TWO STANDARD TREATMENTS IN AUTOLOGOUS STEM CELL TRANSPLANTATION INELIGIBLE POPULATION AFFECTED BY MULTIPLE MYELOMA
NCT06409702	PHASE4	RECRUITING	Treatment of High-risk Newly Diagnosed Multiple Myeloma With Minimal Residual Disease Detection
NCT07025005	PHASE4	RECRUITING	Fenofibrate Role in the Prophylaxis From Peripheral Neuropathy Induced by Bortezomib, Lenalidomide and Dexamethasone (VRd) Protocol in the Treatment of Patients With Multiple Myeloma (MM)
NCT07334535	PHASE4	NOT_YET_RECRUITING	Isa-VRD in TIE HRMM
NCT01198054	PHASE4	TERMINATED	LENA-LMA-5:Lenalidomide in Acute Myeloid Leukemia (AML)
NCT01408199	PHASE4	COMPLETED	Study To Evaluate The Safety And Efficacy Of Lenalidomide For Refractory Cutaneous Lupus
NCT01731886	PHASE4	COMPLETED	Lenalidomide and Dexamethasone With/Without Stem Cell Transplant in Patients With Multiple Myeloma
NCT03173092	PHASE4	TERMINATED	A Study of Ixazomib (NINLARO®) in Combination With Lenalidomide and Dexamethasone (IRD) for the Treatment of Participants With Multiple Myeloma (MM)
NCT03416374	PHASE4	COMPLETED	A Study to Evaluate the Efficacy and Safety of Ixazomib in Combination With Lenalidomide and Dexamethasone in Patients With Relapsed and/or Refractory Multiple Myeloma Initially Treated With an Injection of Proteasome Inhibitor-Based Therapy
NCT03934684	PHASE4	COMPLETED	Study to Evaluate Safety Tolerability & Efficacy of Kyprolis (Carfilzomib) in Relapsed or Refractory Multiple Myeloma
NCT04217967	PHASE4	COMPLETED	Ixazomib, Lenalidomide, and Combination for Maintenance in NDMM Patients
NCT05183139	PHASE4	WITHDRAWN	A Multicenter In-class Transition Study of Ixazomib Combined With Pomalidomide and Dexamethasone or With Lenalidomide and Dexamethasone in Adults With Relapsed/Refractory Multiple Myeloma
NCT05598580	PHASE4	UNKNOWN	Immunomodulators on HIV-1 Reservoir
NCT06004765	PHASE4	UNKNOWN	Efficacy and Safety of Lenalidomide Combined With Azacitidine vs Azacitidine in the Treatment of MDS-RS
NCT00098475	PHASE3	ACTIVE_NOT_RECRUITING	Lenalidomide and Dexamethasone With or Without Thalidomide in Treating Patients With Multiple Myeloma
NCT00114101	PHASE3	ACTIVE_NOT_RECRUITING	Lenalidomide in Treating Patients With Multiple Myeloma Undergoing Autologous Stem Cell Transplant
NCT00602641	PHASE3	ACTIVE_NOT_RECRUITING	Melphalan, Prednisone, and Thalidomide or Lenalidomide in Treating Patients With Newly Diagnosed Multiple Myeloma
NCT00644228	PHASE3	ACTIVE_NOT_RECRUITING	Lenalidomide and Dexamethasone With or Without Bortezomib in Treating Patients With Previously Untreated Multiple Myeloma
NCT00843882	PHASE3	ACTIVE_NOT_RECRUITING	Lenalidomide With or Without Epoetin Alfa in Treating Patients With Myelodysplastic Syndrome and Anemia
NCT01169337	PHASE3	ACTIVE_NOT_RECRUITING	Lenalidomide or Observation in Treating Patients With Asymptomatic High-Risk Smoldering Multiple Myeloma
NCT01208662	PHASE3	ACTIVE_NOT_RECRUITING	Randomized Trial of Lenalidomide, Bortezomib, Dexamethasone vs High-Dose Treatment With SCT in MM Patients up to Age 65
NCT01863550	PHASE3	ACTIVE_NOT_RECRUITING	Bortezomib or Carfilzomib With Lenalidomide and Dexamethasone in Treating Patients With Newly Diagnosed Multiple Myeloma
NCT02544308	PHASE3	ACTIVE_NOT_RECRUITING	Trial of Immunomodulatory Therapy in High Risk Solitary Bone Plasmacytoma
NCT02659293	PHASE3	ACTIVE_NOT_RECRUITING	Trial of Carfilzomib, Lenalidomide, Dexamethasone Versus Lenalidomide Alone After Stem-cell Transplant for Multiple Myeloma
NCT03319667	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Investigate the Clinical Benefit of Isatuximab in Combination With Bortezomib, Lenalidomide and Dexamethasone in Adults With Newly Diagnosed Multiple Myeloma Not Eligible for Transplant
NCT03617731	PHASE3	ACTIVE_NOT_RECRUITING	Trial on the Effect of Isatuximab to Lenalidomide/Bortezomib/Dexamethasone (RVd) Induction and Lenalidomide Maintenance in Patients With Newly Diagnosed Myeloma (GMMG HD7)
NCT03651128	PHASE3	ACTIVE_NOT_RECRUITING	Efficacy and Safety Study of bb2121 Versus Standard Regimens in Subjects With Relapsed and Refractory Multiple Myeloma (RRMM)
NCT03652064	PHASE3	ACTIVE_NOT_RECRUITING	A Study Comparing Daratumumab, VELCADE (Bortezomib), Lenalidomide, and Dexamethasone (D-VRd) With VELCADE, Lenalidomide, and Dexamethasone (VRd) in Participants With Untreated Multiple Myeloma and for Whom Hematopoietic Stem Cell Transplant is Not Planned as Initial Therapy
NCT03710603	PHASE3	ACTIVE_NOT_RECRUITING	Daratumumab, VELCADE (Bortezomib), Lenalidomide and Dexamethasone Compared to VELCADE, Lenalidomide and Dexamethasone in Subjects With Previously Untreated Multiple Myeloma
NCT03729804	PHASE3	ACTIVE_NOT_RECRUITING	Carfilzomib, Lenalidomide, and Dexamethasone Versus Bortezomib, Lenalidomide and Dexamethasone (KRd vs. VRd) in Patients With Newly Diagnosed Multiple Myeloma (COBRA)
NCT03836014	PHASE3	ACTIVE_NOT_RECRUITING	Study Comparing Continuous Versus Fixed Duration Therapy With Daratumumab, Lenalidomide, and Dexamethasone for Relapsed Multiple Myeloma
NCT03901963	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Daratumumab Plus Lenalidomide Versus Lenalidomide Alone as Maintenance Treatment in Participants With Newly Diagnosed Multiple Myeloma Who Are Minimal Residual Disease Positive After Frontline Autologous Stem Cell Transplant
NCT03937635	PHASE3	RECRUITING	Lenalidomide, and Dexamethasone With or Without Daratumumab in Treating Patients With High-Risk Smoldering Myeloma
NCT03948035	PHASE3	ACTIVE_NOT_RECRUITING	Elotuzumab in Combination With Carfilzomib, Lenalidomide and Dexamethasone (E-KRd) Versus KRd in MM
NCT04071457	PHASE3	ACTIVE_NOT_RECRUITING	S1803, Lenalidomide +/- Daratumumab/rHuPh20 as Post-ASCT Maintenance for MM w/MRD to Direct Therapy Duration
NCT04096066	PHASE3	ACTIVE_NOT_RECRUITING	A Trial That Compare Two Treatments in Newly Diagnosed Myeloma Patients Not Eligible for Transplant
NCT04224493	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Assess the Efficacy, Safety, Pharmacodynamics, and Pharmacokinetics of Tazemetostat in Combination With Lenalidomide Plus Rituximab Versus Placebo in Combination With Lenalidomide Plus Rituximab in Adult Patients at Least 18 Years of Age With Relapsed/Refractory Follicular Lymphoma.
NCT04270409	PHASE3	ACTIVE_NOT_RECRUITING	Isatuximab in Combination With Lenalidomide and Dexamethasone in High-risk Smoldering Multiple Myeloma
NCT04404283	PHASE3	ACTIVE_NOT_RECRUITING	Brentuximab Vedotin Plus Lenalidomide and Rituximab for the Treatment of Relapsed/Refractory DLBCL
NCT04566328	PHASE3	RECRUITING	Testing the Use of Combination Therapy in Adult Patients With Newly Diagnosed Multiple Myeloma, the EQUATE Trial

Clinical evidence (CIViC)

Variant × indication × effect (1 predictive associations from 1 curated evidence items):

Variant	Indication	Effect	Therapy	Level	CIViC
CRBN Mutation	Multiple Myeloma	Resistance	Lenalidomide + Pomalidomide	CIViC C	EID1766

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 4 clinical and 23 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

18 molecules share ≥1 primary target. Top 18 by shared-target count:

Molecule	Source	Status	Shared targets
CRIZOTINIB	ChEMBL + PubChem	Phase 4 (approved)	CRBN
POMALIDOMIDE	ChEMBL + PubChem	Phase 4 (approved)	CRBN
ASCIMINIB	ChEMBL	Phase 4 (approved)	CRBN
BRIGATINIB	ChEMBL	Phase 4 (approved)	CRBN
DASABUVIR	ChEMBL	Phase 4 (approved)	CRBN
PONATINIB	ChEMBL	Phase 4 (approved)	CRBN
THALIDOMIDE	ChEMBL	Phase 4 (approved)	CRBN
IBERDOMIDE	ChEMBL	Phase 3	CRBN
MEZIGDOMIDE	ChEMBL	Phase 3	CRBN
URACIL	ChEMBL	Phase 3	CRBN
VEPDEGESTRANT	ChEMBL	Phase 3	CRBN
ADAVOSERTIB	ChEMBL	Phase 2	CRBN
AVADOMIDE	ChEMBL	Phase 2	CRBN
E-7820	ChEMBL	Phase 2	CRBN
FORETINIB	ChEMBL	Phase 2	CRBN
INDISULAM	ChEMBL	Phase 2	CRBN
Fulvestrant	PubChem	Approved	CRBN
Sotorasib	PubChem	Approved	CRBN