Tirbanibulin

Summary

Tirbanibulin (CHEMBL571546) is an approved small-molecule antineoplastic agent (ATC D06BX03) targeting SRC; indicated across 6 conditions including actinic keratosis and basal cell carcinoma; with CIViC clinical evidence for 1 variant-indication association (e.g. FLT3 ITD AND FLT3 F691L in acute myeloid leukemia).

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: D06BX03
• Targets: 1 (SRC)
• Indications: 6 conditions
• Clinical trials: 12
• Precision-oncology evidence (CIViC): 1 variant–indication association
• Chemistry: 431.5 Da · C26H29N3O3

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL571546
Name	Tirbanibulin
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	23635314
ChEBI	CHEBI:231702
ATC	D06BX03
Molecular formula	C26H29N3O3
Molecular weight	431.5
InChIKey	HUNGUWOZPQBXGX-UHFFFAOYSA-N

SMILES: C1COCCN1CCOC2=CC=C(C=C2)C3=CN=C(C=C3)CC(=O)NCC4=CC=CC=C4

IUPAC name: N-benzyl-2-[5-[4-(2-morpholin-4-ylethoxy)phenyl]-2-pyridinyl]acetamide

ChEBI definition: A member of the class of pyridines that is pyridine substituted by 2-(benzylamino)-2-oxoethyl and 4-[2-(morpholin-4-yl)ethoxy]phenyl groups at positions 2 and 5, respectively. It is a dual inhibitor of Src kinase and tubulin and approved by the FDA for the topical treatment of actinic keratosis on the face or scalp.

Pharmacological roles (ChEBI): antineoplastic agent, apoptosis inducer, EC 2.7.10.2 (non-specific protein-tyrosine kinase) inhibitor, microtubule-destabilising agent.

Also known as: Klisyri, KX-01, KX-2391, KX01, KX2391, Tirbanibulin, Tirbanibulina, Tirbanibuline, SID164339429, TIRBANIBULIN, Klisyri; Tirbanibulin

Parent form; salt/anhydrous children: CHEMBL4594279

Patent coverage: 459 distinct patent families (1,192 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 1,047 (88%) 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
SRC	SRC proto-oncogene, non-receptor tyrosine kinase	Inhibition	4.34	3.7%	P12931

Broader ChEMBL bioactivity targets: 4 (assay-derived). Sample: Tubulin, Bcr/Abl fusion protein, Proto-oncogene tyrosine-protein kinase Src, Tyrosine-protein kinase Lyn.

Bioactivity

ChEMBL activities: 6 potent at pChembl ≥ 5 of 8 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
SRC	8.19	IC50	6.5	nM	CHEMBL_ACT_19114101
SRC	7.89	IC50	13	nM	CHEMBL_ACT_19114089
SRC	7.7	IC50	20	nM	CHEMBL_ACT_6175412
ABL1	7	IC50	100	nM	CHEMBL_ACT_19114111
LYN	7	IC50	100	nM	CHEMBL_ACT_19114126
TUBB4A	5.96	Kd	1110	nM	CHEMBL_ACT_24359813

Target pathways

Aggregated over 1 target gene(s): SRC.

Top Reactome pathways

121 total, by targets touching each:

Pathway	Targets	Genes
Hemostasis	1	SRC
Neurotransmitter receptors and postsynaptic signal transmission	1	SRC
Transmission across Chemical Synapses	1	SRC
Neuronal System	1	SRC
Signaling by ERBB2	1	SRC
Signaling by ERBB4	1	SRC
Nuclear signaling by ERBB4	1	SRC
Downregulation of ERBB4 signaling	1	SRC
PIP3 activates AKT signaling	1	SRC
Developmental Biology	1	SRC
Cytokine Signaling in Immune system	1	SRC
Spry regulation of FGF signaling	1	SRC
Signaling by SCF-KIT	1	SRC
Regulation of KIT signaling	1	SRC
Signal Transduction	1	SRC
Disease	1	SRC
Signaling by NTRKs	1	SRC
Immune System	1	SRC
p38MAPK events	1	SRC
Signaling by EGFR	1	SRC
GAB1 signalosome	1	SRC
Downstream signal transduction	1	SRC
Signaling by PDGF	1	SRC
Regulation of gap junction activity	1	SRC
Signaling by Rho GTPases	1	SRC
Negative regulation of the PI3K/AKT network	1	SRC
Signaling by ALK	1	SRC
FCGR activation	1	SRC
PECAM1 interactions	1	SRC
Generic Transcription Pathway	1	SRC

Dominant GO biological processes

GO term	Targets
negative regulation of transcription by RNA polymerase II	1
stimulatory C-type lectin receptor signaling pathway	1
negative regulation of inflammatory response to antigenic stimulus	1
cell adhesion	1
signal transduction	1
signal complex assembly	1
epidermal growth factor receptor signaling pathway	1
transforming growth factor beta receptor signaling pathway	1
integrin-mediated signaling pathway	1
regulation of epithelial cell migration	1
positive regulation of epithelial cell migration	1
positive regulation of protein processing	1
macroautophagy	1
peptidyl-tyrosine phosphorylation	1
regulation of cell-cell adhesion	1

Indications & clinical

Indications

6 indications (1 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
actinic keratosis	4	MONDO:0005173	EFO:0002496
basal cell carcinoma	2	MONDO:0020804	EFO:0004193
acute myeloid leukemia	1	MONDO:0018874	EFO:0000222
lymphoma	1	MONDO:0005062	EFO:0000574
neoplasm	1	MONDO:0005070	EFO:0000616

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

Clinical trials

Total trials: 12.

Phase distribution

Phase	Trials
PHASE1	4
PHASE4	2
PHASE3	2
PHASE2	2
PHASE1/PHASE2	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05900258	PHASE4	COMPLETED	Tirbanibulin 1% Ointment for the Treatment of Chronically Sun-damaged Skin on the Face
NCT06026358	PHASE4	WITHDRAWN	Tirbanibulin 1% Ointment for the Treatment of Actinic Keratosis on the Back of the Hands
NCT07273656	PHASE3	NOT_YET_RECRUITING	Efficacy and Safety of Cryotherapy Followed by Tirbanibulin Ointment for Actinic Keratosis on the Scalp and Forehead
NCT06135415	PHASE3	COMPLETED	A Study to Evaluate the Efficacy and Safety of Tirbanibulin Ointment in Adult Participants With Actinic Keratosis
NCT01074138	PHASE2	COMPLETED	Safety and Efficacy Study of KX2-391 for Treatment of Bone-Metastatic, Castration-Resistant Prostate Cancer
NCT01764087	PHASE1/PHASE2	UNKNOWN	A Study of KX2-391 With Paclitaxel in Patients With Solid Tumors
NCT06112522	PHASE2	UNKNOWN	Tirbanubulin (Klisiry®) in the Treatment of Basal Cell Carcinoma
NCT00658970	PHASE1	COMPLETED	Evaluation of KX2-391 in Patients With Advanced Malignancies
NCT01397799	PHASE1	COMPLETED	Evaluation of KX2-391 in Elderly Subjects With Acute Myeloid Leukemia (AML)
NCT02337205	PHASE1	COMPLETED	Ph 1, Single-Center, Safety, Tolerability & Pharmacokinetic Study of KX2 391 Ointment in Subj. w Actinic Keratosis
NCT05522816	PHASE1	COMPLETED	KX01 Ointment Phase 1 Study in Patients With Plaque Type Psoriasis
NCT05260073	Not specified	COMPLETED	Patient and Clinician Reported Outcomes for Tirbanibulin Effectiveness and Safety in Actinic Keratosis

Clinical evidence (CIViC)

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

Variant	Indication	Effect	Therapy	Level	CIViC
FLT3 ITD AND FLT3 F691L	Acute Myeloid Leukemia	Sensitivity/Response	Tirbanibulin	CIViC D	EID9774

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.

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

Molecule	Source	Status	Shared targets
AFATINIB	ChEMBL + PubChem	Phase 4 (approved)	SRC
CRIZOTINIB	ChEMBL + PubChem	Phase 4 (approved)	SRC
DACOMITINIB	ChEMBL + PubChem	Phase 4 (approved)	SRC
PAZOPANIB	ChEMBL + PubChem	Phase 4 (approved)	SRC
ADENOSINE	ChEMBL	Phase 4 (approved)	SRC
BOSUTINIB	ChEMBL	Phase 4 (approved)	SRC
BRIGATINIB	ChEMBL	Phase 4 (approved)	SRC
CABOZANTINIB	ChEMBL	Phase 4 (approved)	SRC
CERITINIB	ChEMBL	Phase 4 (approved)	SRC
DASATINIB	ChEMBL	Phase 4 (approved)	SRC
ENTRECTINIB	ChEMBL	Phase 4 (approved)	SRC
ERLOTINIB	ChEMBL	Phase 4 (approved)	SRC
FEDRATINIB	ChEMBL	Phase 4 (approved)	SRC
GEFITINIB	ChEMBL	Phase 4 (approved)	SRC
IBRUTINIB	ChEMBL	Phase 4 (approved)	SRC
IMATINIB	ChEMBL	Phase 4 (approved)	SRC
INFIGRATINIB	ChEMBL	Phase 4 (approved)	SRC
LAPATINIB	ChEMBL	Phase 4 (approved)	SRC
MIDOSTAURIN	ChEMBL	Phase 4 (approved)	SRC
NERATINIB	ChEMBL	Phase 4 (approved)	SRC
NICLOSAMIDE	ChEMBL	Phase 4 (approved)	SRC
NILOTINIB	ChEMBL	Phase 4 (approved)	SRC
NINTEDANIB	ChEMBL	Phase 4 (approved)	SRC
PONATINIB	ChEMBL	Phase 4 (approved)	SRC
REPOTRECTINIB	ChEMBL	Phase 4 (approved)	SRC
SORAFENIB	ChEMBL	Phase 4 (approved)	SRC
SUNITINIB	ChEMBL	Phase 4 (approved)	SRC
TIVOZANIB	ChEMBL	Phase 4 (approved)	SRC
VANDETANIB	ChEMBL	Phase 4 (approved)	SRC
ALISERTIB	ChEMBL	Phase 3	SRC
ALVOCIDIB	ChEMBL	Phase 3	SRC
BRIVANIB	ChEMBL	Phase 3	SRC
CANERTINIB	ChEMBL	Phase 3	SRC
CEDIRANIB	ChEMBL	Phase 3	SRC
DOVITINIB	ChEMBL	Phase 3	SRC
INDIGO	ChEMBL	Phase 3	SRC
LESTAURTINIB	ChEMBL	Phase 3	SRC
LINIFANIB	ChEMBL	Phase 3	SRC
MASITINIB	ChEMBL	Phase 3	SRC
QUERCETIN	ChEMBL	Phase 3	SRC
SARACATINIB	ChEMBL	Phase 3	SRC
SEMAXANIB	ChEMBL	Phase 3	SRC
TESEVATINIB	ChEMBL	Phase 3	SRC
AT-9283	ChEMBL	Phase 2	SRC
AZD-3759	ChEMBL	Phase 2	SRC
AZD-6482	ChEMBL	Phase 2	SRC
AZM-475271	ChEMBL	Phase 2	SRC
BEMCENTINIB	ChEMBL	Phase 2	SRC
BIIB-091	ChEMBL	Phase 2	SRC
BMS-690514	ChEMBL	Phase 2	SRC
BMS-754807	ChEMBL	Phase 2	SRC
BMS-986142	ChEMBL	Phase 2	SRC
CENISERTIB	ChEMBL	Phase 2	SRC
CEP-11981	ChEMBL	Phase 2	SRC
DALMELITINIB	ChEMBL	Phase 2	SRC
DANUSERTIB	ChEMBL	Phase 2	SRC
DORAMAPIMOD	ChEMBL	Phase 2	SRC
ELLAGIC ACID	ChEMBL	Phase 2	SRC
ELZOVANTINIB	ChEMBL	Phase 2	SRC
ENMD-2076	ChEMBL	Phase 2	SRC