Sitokiren

Summary

Sitokiren (CHEMBL4110551) is a phase-3 clinical-stage small molecule targeting REN; indicated across 4 conditions including essential hypertension and hypertensive disorder.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 1 (REN)
• Indications: 4 conditions
• Clinical trials: 8
• Chemistry: 444.5 Da · C22H32N6O4

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL4110551
Name	Sitokiren
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	117877477
Molecular formula	C22H32N6O4
Molecular weight	444.5
InChIKey	GRTDDIZIUSADLD-CRAIPNDOSA-N

SMILES: CC1=NC2=C(C=C1)C(=NN2CCCNC(=O)OC)[C@@H](C)N(C3CC3)C(=O)[C@H]4CNCCO4

IUPAC name: methyl N-[3-[3-[(1R)-1-[cyclopropyl-[(2R)-morpholine-2-carbonyl]amino]ethyl]-6-methylpyrazolo[5,4-b]pyridin-1-yl]propyl]carbamate

Also known as: Sitokiren, Sitokirene, Sitokireno, Sph-3127, SPH-3127, Sph3127, SPH3127, SITOKIREN, SITOKIRENE, SITOKIRENO, US9278944, 270

Patent coverage: 6 distinct patent families (12 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 10 (83%) 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
REN	renin	Inhibition	9.4	0.2%	P00797

Broader ChEMBL bioactivity targets: 1 (assay-derived). Sample: Renin.

Bioactivity

ChEMBL activities: 4 potent at pChembl ≥ 5 of 4 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
REN	9.4	IC50	0.4	nM	CHEMBL_ACT_17748597
REN	9.4	IC50	0.4	nM	CHEMBL_ACT_24828079
REN	9.4	IC50	0.4	nM	CHEMBL_ACT_27081857
REN	9.35	IC50	0.45	nM	CHEMBL_ACT_24828090

Target pathways

Aggregated over 1 target gene(s): REN.

Top Reactome pathways

1 total, by targets touching each:

Pathway	Targets	Genes
Metabolism of Angiotensinogen to Angiotensins	1	REN

Dominant GO biological processes

GO term	Targets
kidney development	1
mesonephros development	1
angiotensin maturation	1
renin-angiotensin regulation of aldosterone production	1
proteolysis	1
regulation of blood pressure	1
male gonad development	1
hormone-mediated signaling pathway	1
response to lipopolysaccharide	1
response to immobilization stress	1
drinking behavior	1
regulation of MAPK cascade	1
cell maturation	1
amyloid-beta metabolic process	1
response to cAMP	1

Indications & clinical

Indications

4 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
essential hypertension	3	MONDO:0001134	MONDO:0001134
hypertensive disorder	2	MONDO:0005044	EFO:0000537
ulcerative colitis	2	MONDO:0005101	EFO:0000729
diabetic kidney disease	2	MONDO:0005016	EFO:0000401

Clinical trials

Total trials: 8.

Phase distribution

Phase	Trials
PHASE2	3
PHASE1/PHASE2	2
PHASE1	2
PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05359068	PHASE3	COMPLETED	Study to Evaluate the Efficacy and Safety of SPH3127 In Patients With Mild-moderate Essential Hypertension
NCT05019742	PHASE2	TERMINATED	Evaluation of SPH3127 in Patients With Mild-to-Moderate Ulcerative Colitis
NCT05359055	PHASE1/PHASE2	COMPLETED	Drug-drug Interaction Study of SPH3127
NCT05593562	PHASE1/PHASE2	COMPLETED	Study on Human Mass Balance of SPH3127 Tablets
NCT05593575	PHASE2	COMPLETED	Efficacy and Safety of SPH3127 Tablets on Treating the Diabetic Kidney Disease
NCT05770609	PHASE2	COMPLETED	A Study of SPH3127 in the Treatment of Mild to Moderate Ulcerative Colitis
NCT03128138	PHASE1	COMPLETED	Single Ascending Dose Study of Safety and Tolerability of SPH3127 Tablet in Chinese Healthy Volunteers
NCT03255993	PHASE1	COMPLETED	The Tolerability and Pharmacokinetics of Multiple Doses of SPH3127 in Chinese Healthy People

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.

9 molecules share ≥1 primary target. Top 9 by shared-target count:

Molecule	Source	Status	Shared targets
ALISKIREN	ChEMBL	Phase 4 (approved)	REN
CAPTOPRIL	ChEMBL	Phase 4 (approved)	REN
DITEKIREN	ChEMBL	Phase 2	REN
ENALKIREN	ChEMBL	Phase 2	REN
IMARIKIREN	ChEMBL	Phase 2	REN
PEPSTATIN	ChEMBL	Phase 2	REN
REMIKIREN	ChEMBL	Phase 2	REN
TERLAKIREN	ChEMBL	Phase 2	REN
ZANKIREN	ChEMBL	Phase 2	REN