Fruquintinib
{{Short description|Medication}}
{{Use American English|date=November 2023}}
{{Use dmy dates|date=November 2023}}
{{cs1 config |name-list-style=vanc |display-authors=6}}
{{Infobox drug
| image = Fruquintinib.svg
| width =
| alt =
| caption =
| pronounce =
| tradename = Fruzaqla
| Drugs.com = {{drugs.com|monograph|fruquintinib}}
| MedlinePlus = a623060
| DailyMedID = Fruquintinib
| pregnancy_AU = D
| pregnancy_AU_comment = http://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent=&id=CP-2024-PI-02658-1
| pregnancy_category =
| routes_of_administration = By mouth
| class = Antineoplastic
| ATC_prefix = L01
| ATC_suffix = EK04
| ATC_supplemental =
| biosimilars =
| legal_AU = S4
| legal_AU_comment = {{cite web | title=Fruzaqla (Takeda Pharmaceuticals Australia Pty Ltd) | website=Therapeutic Goods Administration (TGA) | date=9 December 2024 | url=https://www.tga.gov.au/resources/prescription-medicines-registrations/fruzaqla-takeda-pharmaceuticals-australia-pty-ltd | access-date=19 December 2024}}{{cite web | title=Fruzaqla fruquintinib 1 mg hard capsule bottle (422039) | website=Therapeutic Goods Administration (TGA) | date=3 October 2024 | url=https://www.tga.gov.au/resources/artg/422039 | access-date=19 December 2024}}
| legal_BR =
| legal_BR_comment =
| legal_CA = Rx-only
| legal_CA_comment = {{cite web | title=Summary Basis of Decision for Fruzaqla | website=Drug and Health Products Portal | date=2 January 2025 | url=https://dhpp.hpfb-dgpsa.ca/review-documents/resource/SBD1734969149034 | access-date=25 January 2025}}{{cite web | title=Fruzaqla product information | website=Health Canada | date=11 October 2024 | url=https://health-products.canada.ca/dpd-bdpp/info?lang=eng&code=104019 | access-date=27 December 2024}}
| legal_DE =
| legal_DE_comment =
| legal_NZ =
| legal_NZ_comment =
| legal_UK =
| legal_UK_comment =
| legal_US = Rx-only
| legal_EU = Rx-only
| legal_UN =
| legal_UN_comment =
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| bioavailability =
| protein_bound = Plasma protein binding of fruquintinib is approximately 95%.
| metabolism = Fruquintinib is primarily eliminated by CYP450 and non-CYP450 (i.e., sulfation and glucuronidation) metabolism. CYP3A and to a lesser extent CYP2C8, CYP2C9, and CYP2C19 are the CYP450 enzymes involved in fruquintinib metabolism.
| metabolites = The potency of M11 for inhibiting VEGFR-2 kinase activity is 10 times lower than that of fruquintinib (Takeda data on file); therefore, M11 is not considered an active metabolite.
| onset =
| elimination_half-life = 42hr
| duration_of_action =
| excretion = A previous study reported that following administration of 5 mg of radiolabeled fruquintinib, approximately 60% of the dose was recovered in urine (0.50% unchanged) and 30% was recovered in feces (5.34% unchanged), with the remaining radioactivity excreted as metabolites.
| CAS_number = 1194506-26-7
| CAS_supplemental =
| PubChem = 44480399
| IUPHAR_ligand = 9428
| DrugBank = DB11679
| ChemSpiderID = 39625837
| UNII = 49DXG3M5ZW
| KEGG = D11977
| ChEBI = 229221
| ChEMBL = 4303214
| NIAID_ChemDB =
| PDB_ligand =
| synonyms = HMPL-013
| IUPAC_name = 6-[(6,7-dimethoxyquinazolin-4-yl)oxy]-N,2-dimethyl-1-benzofuran-3-carboxamide
| C = 21
| H = 19
| N = 3
| O = 5
| SMILES = CNC(=O)C1=C(C)OC2=CC(OC3=NC=NC4=CC(OC)=C(OC)C=C34)=CC=C12
| StdInChI = 1S/C21H19N3O5/c1-11-19(20(25)22-2)13-6-5-12(7-16(13)28-11)29-21-14-8-17(26-3)18(27-4)9-15(14)23-10-24-21/h5-10H,1-4H3,(H,22,25)
| StdInChI_comment =
| StdInChIKey = BALLNEJQLSTPIO-UHFFFAOYSA-N
| density =
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| solubility = The aqueous
solubility of fruquintinib is pH-dependent, with a solubility of 0.9 μg/mL at pH 6.8 that increases under
acidic conditions to 129.9 μg/mL at pH 1.
Fruquintinib is soluble in organic solvents such
as DMSO and dimethyl formamide (DMF). The solubility of fruquintinib in these solvents is approximately
2 and 5 mg/ml, respectively. https://cdn.caymanchem.com/cdn/insert/29425.pdf
| sol_units =
| specific_rotation =
}}
Fruquintinib, sold under the brand name Fruzaqla, is an anti-cancer medication used for the treatment of colorectal cancer. Fruquintinib is a kinase inhibitor. It is taken by mouth.
The most common adverse reactions include hypertension, palmar-plantar erythrodysesthesia, proteinuria, dysphonia, abdominal pain, diarrhea, and asthenia.
Fruquintinib was approved for medical use in the United States in November 2023.{{cite web | title=FDA approves fruquintinib in refractory metastatic colorectal cancer | website=U.S. Food and Drug Administration (FDA) | date=8 November 2023 | url=https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-fruquintinib-refractory-metastatic-colorectal-cancer | access-date=10 November 2023 | archive-date=10 November 2023 | archive-url=https://web.archive.org/web/20231110020715/https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-fruquintinib-refractory-metastatic-colorectal-cancer | url-status=live }} {{PD-notice}}{{cite press release | title=Takeda Receives U.S. FDA Approval of Fruzaqla (fruquintinib) for Previously Treated Metastatic Colorectal Cancer | publisher=Takeda | via=Business Wire | date=8 November 2023 | url=https://www.businesswire.com/news/home/20231108735203/en/Takeda-Receives-U.S.-FDA-Approval-of-FRUZAQLA%E2%84%A2-fruquintinib-for-Previously-Treated-Metastatic-Colorectal-Cancer | access-date=10 November 2023 | archive-date=8 November 2023 | archive-url=https://web.archive.org/web/20231108232956/https://www.businesswire.com/news/home/20231108735203/en/Takeda-Receives-U.S.-FDA-Approval-of-FRUZAQLA%E2%84%A2-fruquintinib-for-Previously-Treated-Metastatic-Colorectal-Cancer | url-status=live }}
Medical uses
Fruquintinib is indicated for adults with metastatic colorectal cancer who received prior fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if RAS wild-type and medically appropriate, an anti-EGFR therapy.{{cite journal | vauthors = Xu X, Yu Y, Liu M, Liang L, Liu T | title = Efficacy and safety of regorafenib and fruquintinib as third-line treatment for colorectal cancer: a narrative review | journal = Translational Cancer Research | volume = 11 | issue = 1 | pages = 276–287 | date = January 2022 | pmid = 35261903 | pmc = 8841594 | doi = 10.21037/tcr-20-3539 | doi-access = free }}{{cite journal | vauthors = Lavacchi D, Roviello G, Guidolin A, Romano S, Venturini J, Caliman E, Vannini A, Giommoni E, Pellegrini E, Brugia M, Pillozzi S, Antonuzzo L | title = Evaluation of Fruquintinib in the Continuum of Care of Patients with Colorectal Cancer | journal = International Journal of Molecular Sciences | volume = 24 | issue = 6 | date = March 2023 | page = 5840 | pmid = 36982913 | pmc = 10051170 | doi = 10.3390/ijms24065840 | doi-access = free }}
Pharmacology
The earlier generation small molecule VEGFR inhibitors, such as sunitinib,22 sorafenib,23 regorafenib24 and pazopanib25 suffer from poor kinome selectivity. In fact, many of them inhibit more than 10 kinases at similar potency. {{Cite web |title=Discovery of fruquintinib, a potent and highly selective small molecule inhibitor of VEGFR 1, 2, 3 tyrosine kinases for cancer therapy |url=https://pmc.ncbi.nlm.nih.gov/articles/PMC6701622/}}
Fruquintinib is a highly potent and selective VEGFR 1, 2, 3 inhibitor
Fruquintinib was found to inhibit VEGFR2 (KDR) with an IC50 of 25 nmol/L in the Z-lyte assay. The kinase selectivity of fruquintinib was evaluated against a panel of 253 kinases using [32p-ATP] incorporation assay by Upstate Biotechnology Inc. (UBI) (Fig. 1B). The results showed that fruquintinib inhibited VEGFR family member (VEGFR1, 2, 3) with IC50s of 33 nmol/L, 35 nmol/L and 0.5 nmol/L, respectively with weak inhibition of RET, FGFR-1 and c-kit kinases. No significant inhibition was found against all other kinases at 1 μmol/L
History
Efficacy was evaluated in FRESCO-2 (NCT04322539) and FRESCO (NCT02314819). FRESCO-2 (NCT04322539), an international, multicenter, randomized, double-blind, placebo-controlled trial, evaluated 691 participants with metastatic colorectal cancer who had disease progression during or after prior fluoropyrimidine-, oxaliplatin-, irinotecan-based chemotherapy, an anti-VEGF biological therapy an anti-EGFR biological therapy if RAS wild type, and at least one of trifluridine/tipiracil or regorafenib. FRESCO, a multicenter, placebo-controlled trial conducted in China, evaluated 416 participants with metastatic colorectal cancer who had disease progression during or after prior fluoropyrimidine-, oxaliplatin, and irinotecan-based chemotherapy.
Society and culture
= Legal status =
In April 2024, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Fruzaqla, intended for the treatment of people with previously treated metastatic colorectal cancer (mCRC).{{cite press release | title=Meeting highlights from the Committee for Medicinal Products for Human Use (CHMP) 22-25 April 2024 | website=European Medicines Agency | date=26 April 2024 | url=https://www.ema.europa.eu/en/news/meeting-highlights-committee-medicinal-products-human-use-chmp-22-25-april-2024 | access-date=13 June 2024}} The applicant for this medicinal product is Takeda Pharmaceuticals International AG Ireland Branch.{{cite web | title=Fruzaqla EPAR | website=European Medicines Agency | date=25 April 2024 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/fruzaqla | access-date=27 April 2024}} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged. Fruzaqla was approved for medical use in the United States in June 2024.{{cite web | title=Fruzaqla PI | website=Union Register of medicinal products | date=25 June 2024 | url=https://ec.europa.eu/health/documents/community-register/html/h1827.htm | access-date=26 June 2024}}
References
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External links
- {{ClinicalTrialsGov|NCT04322539|A Study of Efficacy and Safety of Fruquintinib (HMPL-013) in Participants With Metastatic Colorectal Cancer (FRESCO-2)}}
- {{ClinicalTrialsGov|NCT02314819|A Phase III Trial Evaluating Fruquintinib Efficacy and Safety in 3+ Line Colorectal Cancer participants （FRESCO) (FRESCO)}}
{{Targeted cancer therapeutic agents}}
{{Growth factor receptor modulators}}
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Category:Receptor tyrosine kinase inhibitors