KIN-3248

This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

Identification

Generic Name
KIN-3248
DrugBank Accession Number
DB17587
Background

KIN-3248 is a small molecule that targets and inhibits oncogenic fibroblast growth factor receptors (FGFRs). It was designed to mainly target FGFR2 and FGFR3 alterations, which act as oncogenic drivers in 10-20% of cholangiocarcinoma and 20-35% of urothelial cancers, respectively.1 While effective, disease progression may occur 6 to 8 months after treatment with currently approved FGFR inhibitors is started, and this effect is usually associated with on-target resistance mutations in the kinase domain of FGFR. Therefore, the broad inhibition of FGFR isoforms may be effective against different types of tumors.1,5 The safety, tolerability, pharmacokinetics, and preliminary efficacy of KIN-3248 are currently being evaluated in adults with advanced tumors harboring FGFR2 and/or FGFR3 gene alterations.3 In February 2023, Kinnate Biopharma received Fast Track designation from the FDA for KIN-3248 to treat unresectable, locally advanced or metastatic cholangiocarcinoma (CCA).4

Type
Small Molecule
Groups
Investigational
Synonyms
Not Available

Pharmacology

Indication

Not Available

Reduce drug development failure rates
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Contraindications & Blackbox Warnings
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Pharmacodynamics

Not Available

Mechanism of action

Fibroblast growth factor receptors (FGFRs) are a subfamily of receptor tyrosine kinases that participate in processes such as embryogenesis, angiogenesis, tissue homeostasis, and wound repair. FGFR signaling is aberrantly activated in different types of cancer. The use of inhibitors that target FGFR represents a therapeutic opportunity; however, mutations on FGFR are the most common mechanism of FGFR-tyrosine kinase inhibitor resistance in targeted therapy.2 KIN-3248 is a pan-FGFR kinase inhibitor that binds to and inhibits the activity of FGFR2 and FGFR3.1,5

TargetActionsOrganism
AFibroblast growth factor receptor 2
inhibitor
Humans
AFibroblast growth factor receptor 3
inhibitor
Humans
Absorption

Not Available

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism
Not Available
Route of elimination

Not Available

Half-life

Not Available

Clearance

Not Available

Adverse Effects
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Toxicity

Not Available

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Not Available
Food Interactions
Not Available

Categories

Drug Categories
Not Available
Classification
Not classified
Affected organisms
Not Available

Chemical Identifiers

UNII
Not Available
CAS number
Not Available
InChI Key
Not Available
InChI
Not Available
IUPAC Name
Not Available
SMILES
Not Available

References

General References
  1. Franovic A, Mohan A, Uryu S, Wu Q, Jiang P, Miller N, Tyhonas J, Timple N, Severson P, Kania R, Murphy E, Bardeesy N, Martin E.: Activity of KIN-3248, a next-generation pan-FGFR inhibitor, against acquired FGFR-gatekeeper and molecular-brake drug resistance mutations J Clin Oncol. 2022 Feb 01;40(suppl 4):461-461. [Article]
  2. Yue S, Li Y, Chen X, Wang J, Li M, Chen Y, Wu D: FGFR-TKI resistance in cancer: current status and perspectives. J Hematol Oncol. 2021 Feb 10;14(1):23. doi: 10.1186/s13045-021-01040-2. [Article]
  3. NCT05242822: A Study to Evaluate KIN-3248 in Participants With Advanced Tumors Harboring FGFR2 and//or FGFR3 Gene Alterations [Link]
  4. Pharmaceutical Technology: Kinnate Biopharma’s CCA therapy KIN-3248 receives FDA Fast Track status [Link]
  5. Kinnate Biopharma: Validated Oncogenic Drivers, An Important Source to Expand Targeted Therapy Access [Link]
Not Available

Clinical Trials

Clinical Trials
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PhaseStatusPurposeConditionsCountStart DateWhy Stopped100+ additional columns
1Active Not RecruitingTreatmentAdult Solid Tumor / Intrahepatic Cholangiocarcinoma / Urothelial Carcinoma1somestatusstop reasonjust information to hide

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Not Available
Experimental Properties
Not Available
Predicted Properties
Not Available
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available
Chromatographic Properties
Collision Cross Sections (CCS)
Not Available

Targets

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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation, migration and apoptosis, and in the regulation of embryonic development. Required for normal embryonic patterning, trophoblast function, limb bud development, lung morphogenesis, osteogenesis and skin development. Plays an essential role in the regulation of osteoblast differentiation, proliferation and apoptosis, and is required for normal skeleton development. Promotes cell proliferation in keratinocytes and immature osteoblasts, but promotes apoptosis in differentiated osteoblasts. Phosphorylates PLCG1, FRS2 and PAK4. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. FGFR2 signaling is down-regulated by ubiquitination, internalization and degradation. Mutations that lead to constitutive kinase activation or impair normal FGFR2 maturation, internalization and degradation lead to aberrant signaling. Over-expressed FGFR2 promotes activation of STAT1.
Specific Function
ATP binding
Gene Name
FGFR2
Uniprot ID
P21802
Uniprot Name
Fibroblast growth factor receptor 2
Molecular Weight
92024.29 Da
References
  1. Franovic A, Mohan A, Uryu S, Wu Q, Jiang P, Miller N, Tyhonas J, Timple N, Severson P, Kania R, Murphy E, Bardeesy N, Martin E.: Activity of KIN-3248, a next-generation pan-FGFR inhibitor, against acquired FGFR-gatekeeper and molecular-brake drug resistance mutations J Clin Oncol. 2022 Feb 01;40(suppl 4):461-461. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation and apoptosis. Plays an essential role in the regulation of chondrocyte differentiation, proliferation and apoptosis, and is required for normal skeleton development. Regulates both osteogenesis and postnatal bone mineralization by osteoblasts. Promotes apoptosis in chondrocytes, but can also promote cancer cell proliferation. Required for normal development of the inner ear. Phosphorylates PLCG1, CBL and FRS2. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Plays a role in the regulation of vitamin D metabolism. Mutations that lead to constitutive kinase activation or impair normal FGFR3 maturation, internalization and degradation lead to aberrant signaling. Over-expressed or constitutively activated FGFR3 promotes activation of PTPN11/SHP2, STAT1, STAT5A and STAT5B. Secreted isoform 3 retains its capacity to bind FGF1 and FGF2 and hence may interfere with FGF signaling
Specific Function
ATP binding
Gene Name
FGFR3
Uniprot ID
P22607
Uniprot Name
Fibroblast growth factor receptor 3
Molecular Weight
87708.905 Da
References
  1. Franovic A, Mohan A, Uryu S, Wu Q, Jiang P, Miller N, Tyhonas J, Timple N, Severson P, Kania R, Murphy E, Bardeesy N, Martin E.: Activity of KIN-3248, a next-generation pan-FGFR inhibitor, against acquired FGFR-gatekeeper and molecular-brake drug resistance mutations J Clin Oncol. 2022 Feb 01;40(suppl 4):461-461. [Article]

Drug created at March 07, 2023 21:51 / Updated at March 11, 2023 21:11