Lorecivivint

Summary

Lorecivivint (CHEMBL4297639) is a phase-3 clinical-stage small molecule targeting CLK2 and DYRK1A; indicated across 3 conditions including osteoarthritis, knee and intervertebral disk degenerative disorder.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 2 (CLK2, DYRK1A)
• Indications: 3 conditions
• Clinical trials: 11
• Chemistry: 505.5 Da · C29H24FN7O

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL4297639
Name	Lorecivivint
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	135565709
Molecular formula	C29H24FN7O
Molecular weight	505.5
InChIKey	AQDWDWAYVBQMAM-UHFFFAOYSA-N

SMILES: CC(C)CC(=O)NC1=CN=CC(=C1)C2=CC3=C(C=C2)NN=C3C4=NC5=C(N4)C=NC=C5C6=CC(=CC=C6)F

IUPAC name: N-[5-[3-[7-(3-fluorophenyl)-3H-imidazo[4,5-c]pyridin-2-yl]-1H-indazol-5-yl]-3-pyridinyl]-3-methylbutanamide

Also known as: Adavivint, Lorecivivint, SM-04690, Sm04690, SM04690, LORECIVIVINT

Patent coverage: 108 distinct patent families (282 SureChEMBL compound mentions), from 5 matched compound structure(s). One matched structure accounts for 197 (70%) 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
CLK2	CDC like kinase 2	Inhibition	8.24	34%	P49760
DYRK1A	dual specificity tyrosine phosphorylation regulated kinase 1A	Inhibition	7.57	10.5%	Q13627

Broader ChEMBL bioactivity targets: 8 (assay-derived). Sample: Dual specificity tyrosine-phosphorylation-regulated kinase 1A, Glycogen synthase kinase-3 beta, Dual specificity protein kinase CLK4, Dual specificity protein kinase CLK1, Dual specificity protein kinase CLK2, Dual specificity protein kinase CLK3, Dual specificity tyrosine-phosphorylation-regulated kinase 2, Dual specificity tyrosine-phosphorylation-regulated kinase 1B.

Bioactivity

ChEMBL activities: 28 potent at pChembl ≥ 5 of 28 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
DYRK1A	8.3	EC50	5	nM	CHEMBL_ACT_22938507
CLK1	8.23	Kd	5.89	nM	CHEMBL_ACT_25065221
CLK2	8.22	EC50	6	nM	CHEMBL_ACT_22939148
CLK2	8.11	IC50	7.8	nM	CHEMBL_ACT_24691610
CLK2	8.11	IC50	7.8	nM	CHEMBL_ACT_25013105
CLK2	8.11	IC50	7.8	nM	CHEMBL_ACT_25900072
CLK2	8.1	IC50	8	nM	CHEMBL_ACT_24863180
CLK2	7.87	IC50	13.6	nM	CHEMBL_ACT_25064364
DYRK1A	7.7	Kd	19.95	nM	CHEMBL_ACT_25065184
CLK4	7.68	IC50	21	nM	CHEMBL_ACT_25900139
DYRK1A	7.57	IC50	26.9	nM	CHEMBL_ACT_24691634
DYRK1A	7.57	IC50	26.9	nM	CHEMBL_ACT_25013133
DYRK1A	7.57	IC50	26.9	nM	CHEMBL_ACT_25900135
DYRK1A	7.52	IC50	30	nM	CHEMBL_ACT_24863181
DYRK1A	7.39	IC50	41.1	nM	CHEMBL_ACT_25065045
CLK3	7.35	IC50	44.3	nM	CHEMBL_ACT_25900099
DYRK1A	7.32	IC50	48	nM	CHEMBL_ACT_25064532
CLK3	7.25	EC50	56	nM	CHEMBL_ACT_22939789
CLK3	7.12	IC50	76.1	nM	CHEMBL_ACT_25064420
DYRK1B	7.05	IC50	89	nM	CHEMBL_ACT_25064588
DYRK1B	7.01	IC50	97.2	nM	CHEMBL_ACT_25065080
GSK3B	6.81	Kd	155.1	nM	CHEMBL_ACT_25065258
CLK4	6.62	IC50	237.7	nM	CHEMBL_ACT_25064476
CLK1	6.62	IC50	239	nM	CHEMBL_ACT_25900138
CLK1	6.61	IC50	246.2	nM	CHEMBL_ACT_25065010
CLK1	6.24	IC50	582.6	nM	CHEMBL_ACT_25064308
GSK3B	6.19	IC50	641.4	nM	CHEMBL_ACT_25064812
DYRK2	5.22	IC50	6049	nM	CHEMBL_ACT_25064644

Target pathways

Aggregated over 2 target gene(s): CLK2, DYRK1A.

Top Reactome pathways

1 total, by targets touching each:

Pathway	Targets	Genes
G0 and Early G1	1	DYRK1A

Dominant GO biological processes

GO term	Targets
protein phosphorylation	2
protein autophosphorylation	2
response to ionizing radiation	1
regulation of RNA splicing	1
negative regulation of gluconeogenesis	1
regulation of alternative mRNA splicing, via spliceosome	1
nervous system development	1
circadian rhythm	1
peptidyl-tyrosine phosphorylation	1
negative regulation of microtubule polymerization	1
negative regulation of heterochromatin formation	1
positive regulation of RNA splicing	1
negative regulation of DNA damage response, signal transduction by p53 class mediator	1
positive regulation of DNA-templated transcription	1
negative regulation of mRNA splicing, via spliceosome	1

Indications & clinical

Indications

3 indications (0 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
osteoarthritis, knee	3	MONDO:0005416	EFO:0004616
osteoarthritis	2	MONDO:0005178	MONDO:0005178
intervertebral disk degenerative disorder	1	MONDO:0011385	HP:0008419

Clinical trials

Total trials: 11.

Phase distribution

Phase	Trials
PHASE3	5
PHASE2	4
PHASE1	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03928184	PHASE3	COMPLETED	Patient-Reported and Radiographic Outcomes in Evaluating Lorecivivint (SM04690) for the Treatment of Knee Osteoarthritis
NCT04385303	PHASE3	COMPLETED	Patient-Reported Outcomes in Evaluating Lorecivivint (SM04690) for Moderate to Severe Knee Osteoarthritis (STRIDES-1)
NCT04520607	PHASE3	TERMINATED	A Long-Term Safety and Efficacy Study of Lorecivivint in Subjects With Osteoarthritis of the Knee
NCT04931667	PHASE3	TERMINATED	3-year, Open-Label Study Evaluating Safety, Tolerability, and Efficacy of Lorecivivint in Knee Osteoarthritis
NCT05603754	PHASE3	COMPLETED	A Study Utilizing Patient-Reported Outcomes to Evaluate the Safety and Efficacy of Lorecivivint (SM04690) for the Treatment of Moderately to Severely Symptomatic Knee Osteoarthritis (STRIDES)
NCT02536833	PHASE2	COMPLETED	A Study Evaluating the Safety, Tolerability, and Efficacy of SM04690 Injected in the Target Knee Joint of Moderately to Severely Symptomatic Osteoarthritis Subjects
NCT03122860	PHASE2	COMPLETED	A Study Evaluating the Safety and Efficacy of SM04690 for the Treatment of Moderately to Severely Symptomatic Knee Osteoarthritis
NCT03706521	PHASE2	TERMINATED	MRI Study to Evaluate the Safety and Efficacy of SM04690 for Knee Osteoarthritis
NCT03727022	PHASE2	COMPLETED	Safety and Bone Health Study of SM04690 for the Treatment of Moderately to Severely Symptomatic Knee Osteoarthritis
NCT03246399	PHASE1	TERMINATED	A Study of the Safety, Tolerability, and Pharmacokinetics of SM04690 Injectable Suspension Following Single Intradiscal Injection in Subjects With Degenerative Disc Disease
NCT04598542	PHASE1	COMPLETED	Drug-Drug Interaction Study of Lorecivivint and Triamcinolone Acetonide in Healthy Volunteers

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

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.

65 molecules share ≥1 primary target. Top 60 by shared-target count:

Molecule	Source	Status	Shared targets
Afatinib	ChEMBL + PubChem	Phase 4 (approved)	CLK2, DYRK1A
BELUMOSUDIL	ChEMBL + PubChem	Phase 4 (approved)	CLK2, DYRK1A
ABEMACICLIB	ChEMBL	Phase 4 (approved)	CLK2, DYRK1A
MIDOSTAURIN	ChEMBL	Phase 4 (approved)	CLK2, DYRK1A
PALBOCICLIB	ChEMBL	Phase 4 (approved)	CLK2, DYRK1A
RUXOLITINIB	ChEMBL	Phase 4 (approved)	CLK2, DYRK1A
SUNITINIB	ChEMBL	Phase 4 (approved)	CLK2, DYRK1A
ALVOCIDIB	ChEMBL	Phase 3	CLK2, DYRK1A
ENZASTAURIN	ChEMBL	Phase 3	CLK2, DYRK1A
EPIGALOCATECHIN GALLATE	ChEMBL	Phase 3	CLK2, DYRK1A
LESTAURTINIB	ChEMBL	Phase 3	CLK2, DYRK1A
RUBOXISTAURIN	ChEMBL	Phase 3	CLK2, DYRK1A
AT-7519	ChEMBL	Phase 2	CLK2, DYRK1A
CC-401	ChEMBL	Phase 2	CLK2, DYRK1A
LY-2090314	ChEMBL	Phase 2	CLK2, DYRK1A
R-406	ChEMBL	Phase 2	CLK2, DYRK1A
RG-547	ChEMBL	Phase 2	CLK2, DYRK1A
SELICICLIB	ChEMBL	Phase 2	CLK2, DYRK1A
SILMITASERTIB	ChEMBL	Phase 2	CLK2, DYRK1A
SU-014813	ChEMBL	Phase 2	CLK2, DYRK1A
TG100-115	ChEMBL	Phase 2	CLK2, DYRK1A
Binimetinib	PubChem	Approved	CLK2, DYRK1A
Crizotinib	PubChem	Approved	CLK2, DYRK1A
dacomitinib	PubChem	Approved	CLK2, DYRK1A
Gefitinib	PubChem	Approved	CLK2, DYRK1A
Idelalisib	PubChem	Approved	CLK2, DYRK1A
Pazopanib	PubChem	Approved	CLK2, DYRK1A
regorafenib	PubChem	Approved	CLK2, DYRK1A
Selumetinib	PubChem	Approved	CLK2, DYRK1A
Trametinib	PubChem	Approved	CLK2, DYRK1A
FEDRATINIB	ChEMBL + PubChem	Phase 4 (approved)	CLK2
AFATINIB DIMALEATE	ChEMBL	Phase 4 (approved)	DYRK1A
ALECTINIB	ChEMBL	Phase 4 (approved)	CLK2
BOSUTINIB	ChEMBL	Phase 4 (approved)	CLK2
BRIGATINIB	ChEMBL	Phase 4 (approved)	CLK2
CHLORHEXIDINE	ChEMBL	Phase 4 (approved)	CLK2
ENTRECTINIB	ChEMBL	Phase 4 (approved)	CLK2
GATIFLOXACIN	ChEMBL	Phase 4 (approved)	CLK2
NINTEDANIB	ChEMBL	Phase 4 (approved)	CLK2
NIRAPARIB	ChEMBL	Phase 4 (approved)	DYRK1A
RUCAPARIB	ChEMBL	Phase 4 (approved)	DYRK1A
TOVORAFENIB	ChEMBL	Phase 4 (approved)	DYRK1A
BARASERTIB	ChEMBL	Phase 3	DYRK1A
CANERTINIB	ChEMBL	Phase 3	DYRK1A
CRENOLANIB	ChEMBL	Phase 3	DYRK1A
CURCUMIN	ChEMBL	Phase 3	DYRK1A
DEFACTINIB	ChEMBL	Phase 3	DYRK1A
DOVITINIB	ChEMBL	Phase 3	CLK2
AT-9283	ChEMBL	Phase 2	DYRK1A
BGT-226 FREE BASE	ChEMBL	Phase 2	DYRK1A
BI-2536	ChEMBL	Phase 2	CLK2
BMS-690514	ChEMBL	Phase 2	DYRK1A
CENISERTIB	ChEMBL	Phase 2	CLK2
MILCICLIB	ChEMBL	Phase 2	DYRK1A
MONZOSERTIB	ChEMBL	Phase 2	CLK2
PELITINIB	ChEMBL	Phase 2	CLK2
PICTILISIB	ChEMBL	Phase 2	CLK2
ROGOCEKIB	ChEMBL	Phase 2	CLK2
SOTRASTAURIN	ChEMBL	Phase 2	CLK2
TANDUTINIB	ChEMBL	Phase 2	CLK2