Claturafenib

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Claturafenib

CAS 2754408-94-9

MF C18H15Cl2F2N5O3S MW490.3 g/mol

N-[2-chloro-3-[(5-chloro-3-methyl-4-oxoquinazolin-6-yl)amino]-4-fluorophenyl]-3-fluoroazetidine-1-sulfonamide

N-{2-chloro-3-[(5-chloro-3-methyl-4-oxo-3,4-dihydroquinazolin-6-yl)amino]-4-fluorophenyl}-3-fluoroazetidine-1-sulfonamide
B-Raf (BRAF) inhibitor, antineoplastic, PF-07799933, PF 07799933, ARRY440, ARRY 440, PC35M52J8T

Claturafenib (development code PF-07799933) is an investigational cancer drug currently being developed by Pfizer. It is a selective, orally active pan-mutant BRAF inhibitor designed to treat advanced solid tumours with specific genetic alterations

Mechanism of Action

Claturafenib belongs to a class of drugs that target the MAPK/ERK signaling pathway, which is often hijacked by cancer cells to promote uncontrolled growth.

Pan-Mutant Inhibition: Unlike first-generation BRAF inhibitors, claturafenib inhibits multiple classes of BRAF mutations, including Class 1 (V600), Class 2, and Class 3 alterations.
Brain-Penetrant: It is designed to cross the blood-brain barrier, allowing it to potentially treat brain metastases or primary brain tumours.
Dimer Disruption: It works by disrupting the formation of BRAF-containing dimers, which are responsible for signaling in many resistant or non-V600 mutant cancers.
Selectivity: It is highly selective for mutant BRAF, significantly sparing normal (wild-type) cells to reduce off-target side effects.

🏥 Clinical Status

As of April 2026, claturafenib is in Phase 1 clinical trials.

Target Indications: Advanced solid malignancies, including melanoma, colorectal cancer (CRC), and non-small cell lung cancer (NSCLC).
Combination Therapy: It is being studied both as a single agent (monotherapy) and in combination with other drugs like binimetinib (a MEK inhibitor) or cetuximab (an EGFR inhibitor).
Ongoing Study: Clinical trial NCT05355701 is currently evaluating its safety, dosage, and efficacy in patients whose disease has progressed on other treatments.
A Study to Learn About the Study Medicine Called PF-07799933 in People With Advanced Solid Tumors With BRAF Alterations.CTID: NCT05355701Phase: Phase 1Status: RecruitingDate: 2026-03-27
A Study to Learn About the Study Medicine Called PF-07799544 as Monotherapy or in Combination in People With Advanced Solid TumorsCTID: NCT05538130Phase: Phase 1Status: RecruitingDate: 2026-03-27

Claturafenib is an orally bioavailable class 1 and 2 inhibitor of the serine/threonine-protein kinase B-raf (BRAF) protein, with potential antineoplastic activity. Upon oral administration, claturafenib selectively binds to and inhibits the activity of class 1 and 2 BRAF alterations. This inhibits the proliferation of tumor cells which express these BRAF alterations. BRAF, a member of the raf family of serine/threonine protein kinases, plays a role in the regulation of mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK) signaling pathways, which may be constitutively activated due to BRAF gene mutations. Mutated forms and fusions of BRAF are associated with a number of neoplastic diseases.

Property	Value
Molecular Formula
Molecular Weight	490.31 g/mol
CAS Number	2754408-94-9
Other Names	ARRY-440, PF07799933

📍 Note: Claturafenib is an investigational compound and has not yet been approved by the FDA or other regulatory agencies for general use

SYN

US12303509,

Example 126

SYN

https://patentscope.wipo.int/search/en/detail.jsf?docId=US374019464&_cid=P12-MO553W-18219-1

Example 126

N-(2-chloro-3-((5-chloro-3-methyl-4-oxo-3,4-dihydroquinazolin-6-yl)amino)-4-fluorophenyl)-3-fluoroazetidine-1-sulfonamide

A solution of 6-amino-5-chloro-3-methylquinazolin-4(3H)-one (90 mg, 0.42 mmol), tert-butyl (2-chloro-4-fluoro-3-iodophenyl)((3-fluoroazetidin-1-yl)sulfonyl)carbamate (218 mg, 0.429 mmol), tris(dibenzylideneacetone)dipalladium (39 mg, 0.042 mmol), Xantphos (62 mg, 0.10 mmol), and cesium carbonate (279 mg, 0.858 mmol) in toluene (2860 μL) was sparged with argon and heated to 110° C. overnight in a sealed vial. The solution was filtered through Celite®, concentrated, and the residue was stirred in 1 mL of DCM and 1 mL of TFA for 1 hour. The solution was concentrated and purified by reverse-phase chromatography (5-95% MeCN/water, 0.1% TFA) and the product was partitioned between DCM and saturated NaHCO ₃. The organic layer was washed with brine, dried over Na ₂SO ₄, filtered, and concentrated to give N-(2-chloro-3-((5-chloro-3-methyl-4-oxo-3,4-dihydroquinazolin-6-yl)amino)-4-fluorophenyl)-3-fluoroazetidine-1-sulfonamide (78 mg, 37% yield). ¹H NMR (400 MHz, CDCl ₃) δ 7.94 (s, 1H), 7.56-7.52 (m, 1H), 7.51 (d, 1H), 7.19-7.14 (t, 1H), 6.99-6.95 (m, 1H), 6.72 (s, br, 1H), 6.47 (s, br, 1H), 5.35-5.15 (m, 1H), 4.25-4.10 (m, 4H), 3.57 (s, 3H); MS (apci, m/z)=490.1, 492.1 (M+H).

PAT