Pemigatinib free base | CAS#1513857-77-6 | tyrosine kinase inhibitor/antineoplastic

MedKoo Cat#: 561861 | Name: Pemigatinib

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Pemigatinib, also known as INCB054828, is an orally bioavailable inhibitor of the fibroblast growth factor receptor (FGFR) types 1, 2, and 3 (FGFR1/2/3), with potential antineoplastic activity. FGFR inhibitor INCB054828 binds to and inhibits FGFR1/2/3, which may result in the inhibition of FGFR1/2/3-related signal transduction pathways. This inhibits proliferation in FGFR1/2/3-overexpressing tumor cells.

Chemical Structure

Pemigatinib

CAS#1513857-77-6 (free base)

Theoretical Analysis

MedKoo Cat#: 561861

Name: Pemigatinib

CAS#: 1513857-77-6 (free base)

Chemical Formula: C24H27F2N5O4

Exact Mass: 487.2031

Molecular Weight: 487.50

Elemental Analysis: C, 59.13; H, 5.58; F, 7.79; N, 14.37; O, 13.13

Price and Availability

Size	Price	Availability
5mg	USD 150.00	Ready to ship
10mg	USD 250.00	Ready to ship
25mg	USD 450.00	Ready to ship
50mg	USD 750.00	Ready to ship
100mg	USD 1,250.00	Ready to ship
200mg	USD 1,950.00	Ready to ship

Bulk Inquiry

Buy Now

Add to Cart

Related CAS #

1513857-77-6 (free base) Pemigatinib HCl

Synonym

Pemigatinib; INCB054828; INCB-054828; INCB 054828; INCB54828; INCB 54828; INCB-54828

IUPAC/Chemical Name

3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-[(morpholin-4-yl)methyl]-1,3,4,7-tetrahydro-2Hpyrrolo[3',2':5,6]pyrido[4,3-d]pyrimidin-2-one

InChi Key

HCDMJFOHIXMBOV-UHFFFAOYSA-N

InChi Code

InChI=1S/C24H27F2N5O4/c1-4-30-21-14(11-27-23-16(21)9-15(28-23)13-29-5-7-35-8-6-29)12-31(24(30)32)22-19(25)17(33-2)10-18(34-3)20(22)26/h9-11H,4-8,12-13H2,1-3H3,(H,27,28)

SMILES Code

O=C1N(CC)C2=C3C(NC(CN4CCOCC4)=C3)=NC=C2CN1C5=C(F)C(OC)=CC(OC)=C5F

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#A20T08K21

QC Data

View QC data: current batch, Lot#A20T08K21

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Pemigatinib (INCB054828) is an orally active, selective FGFR inhibitor with IC50s of 0.4 nM, 0.5 nM, 1.2 nM, 30 nM for FGFR1, FGFR2, FGFR3, FGFR4, respectively.

In vitro activity:

To investigate the effect of INCB054828 treatment on intracellular signaling, Western blot analysis was used for markers of FGFR pathway activation. 2 cell lines were chosen that were derived from malignancies associated with genetically activated FGFR1 (KG1a, 8p11-positive acute myeloid leukemia [AML]) and FGFR3 (RT-4, urothelial carcinoma) that are also indications in which INCB054828 is currently being investigated in phase 2 clinical trials. In the KG1a cell line that bears an FGFR1OP2-FGFR1 translocation, a concentration of greater than 5 nM reduced levels of phospho-FGFR to basal levels (Fig 2A). Phospho-ERK and phospho-STAT5 are also reduced with the same concentration dependence, consistent with potent suppression of FGFR activation by the inhibitor. Treatment of the bladder cancer line RT-4 that harbors an FGFR3-TACC3 translocation with INCB054828 strongly suppresses levels of phospho-FRS2, a scaffolding protein that is a substrate of FGFR, and phospho-ERK (Fig 2B). FGFR3 phosphorylation was not detectable by Western blotting; however, a decrease was detected by proximity ligation assay that uses polymerase chain reaction to amplify the signal from the bound antibodies to phospho- and total FGFR3 (S4 Fig). Using this method, potent inhibition of FGFR3 by INCB054828 (<10 nM) was confirmed in a second urothelial cell line RT-112 that also harbors the FGFR3-TACC3 fusion (Fig 2C). INCB054828 selectively inhibits the growth of tumor cell lines with activation of FGFR signaling (Table 1). The most sensitive lines had GI50 values (concentration required to inhibit growth by 50%) less than 15 nM. In comparison, the GI50 values for a panel of hematologic and solid tumor cell lines that lacked known alterations in the FGFR genes exceeded 2,500 nM (S3 Table); many of these cell lines are known to have dependencies on other oncogenes (e.g. EGFR, HCC-422; K-Ras, A549, and UMUC3). The data reveal a clear separation in sensitivity to INCB054828 between cell lines with genetic alterations in FGFR1, FGFR2, or FGFR3 and cell lines lacking these aberrations. Furthermore, there was no inhibition of the proliferation of primary T cells from normal donors up to 1,500 nM (S5 Fig). Reference: PLoS One. 2020 Apr 21;15(4):e0231877. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/32315352/

In vivo activity:

The antitumor effect of orally dosed INCB054828 was investigated using xenograft tumor models with genetic alterations in FGFR1 (KG1), FGFR2 (KATO III), and FGFR3 (RT-112). A full dose-response was evaluated using the KATO III gastric cancer model harboring genetic amplification of FGFR2 (Fig 4A). A once-daily dose of 0.03 mg/kg INCB054828 significantly suppressed tumor growth while maximum activity was observed at doses equal to or greater than 0.3 mg/kg once daily. The KG1 erythroleukemia AML cell line carries a translocation of FGFR1 (FGFROP2-FGFR1) that has been described in patients with 8p11 myeloproliferative neoplasms. It is the parental line to KG1a, and the in vitro activity of INCB054828 against KG1 and KG1a is similar (GI50 values 1 and 3 nM, respectively). A once-daily dose of 0.3 mg/kg showed significant efficacy (P < 0.05; Fig 4B) against the KG1 subcutaneous xenograft in a humanized mouse NSG mice engrafted with human CD34+ umbilical cord blood cells. Finally, the activity of INCB054828 was evaluated against an FGFR3-dependent model, RT-112 bladder carcinoma that carries the FGFR3-TACC3 fusion. This xenograft model was established subcutaneously into nude rats, and oral administration of 0.3 and 1 mg/kg INCB054828 resulted in significant tumor growth inhibition (Fig 4C). Collectively, these data confirm the balanced activity of INCB054828 against FGFR1, 2, and 3 and show that significant efficacy can be achieved with low daily doses. Plasma levels of INCB054828 showed less than 2-fold variation among the xenograft studies at the 1-mg/kg dose for mouse studies. Reference: PLoS One. 2020 Apr 21;15(4):e0231877. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/32315352/

	Solvent	mg/mL	mM
Solubility
	DMSO	40.0	82.05

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 487.50 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

In vitro protocol:

1. Liu PCC, Koblish H, Wu L, Bowman K, Diamond S, DiMatteo D, Zhang Y, Hansbury M, Rupar M, Wen X, Collier P, Feldman P, Klabe R, Burke KA, Soloviev M, Gardiner C, He X, Volgina A, Covington M, Ruggeri B, Wynn R, Burn TC, Scherle P, Yeleswaram S, Yao W, Huber R, Hollis G. INCB054828 (pemigatinib), a potent and selective inhibitor of fibroblast growth factor receptors 1, 2, and 3, displays activity against genetically defined tumor models. PLoS One. 2020 Apr 21;15(4):e0231877. doi: 10.1371/journal.pone.0231877. PMID: 32315352; PMCID: PMC7313537.

In vivo protocol:

1: Gnagni L, Ruscito I, Zizzari IG, Nuti M, Napoletano C, Rughetti A. Precision oncology targeting FGFRs: A systematic review on pre-clinical activity and clinical outcomes of pemigatinib. Crit Rev Oncol Hematol. 2024 Jul 31;202:104464. doi: 10.1016/j.critrevonc.2024.104464. Epub ahead of print. PMID: 39094670. 2: Saleh M, Barve M, Subbiah V, Papadopoulos KP, Morgensztern D, Mettu NB, Roychowdhury S, Spanggaard I, Veronese ML, Tian C, Silverman IM, Gutierrez M. Open-label, dose-escalation FIGHT-101 study of pemigatinib combined with targeted therapy, chemotherapy, or immunotherapy in patients with advanced malignancies. ESMO Open. 2024 Jul;9(7):103625. doi: 10.1016/j.esmoop.2024.103625. Epub 2024 Jul 9. PMID: 38986210; PMCID: PMC11295983. 3: Kaneko J, Kiuchi R, Takinami M, Ohnishi I, Ito J, Jindo O, Nishino M, Takahashi Y, Yamada T, Sakaguchi T. Successful intrahepatic cholangiocarcinoma conversion surgery after administration of fibroblast growth factor receptor inhibitor. Clin J Gastroenterol. 2024 Jul 10. doi: 10.1007/s12328-024-02014-w. Epub ahead of print. PMID: 38985249. 4: Barmas-Alamdari D, Jiao G, Lieberman R. Case report: Pemigatinib-induced retinopathy: a serial examination of subretinal fluid secondary to an FGFR inhibitor. Front Ophthalmol (Lausanne). 2024 Jan 22;3:1247296. doi: 10.3389/fopht.2023.1247296. PMID: 38983033; PMCID: PMC11182298. 5: Correction to: Recurrent fibroblast growth factor receptor3 fusion glioblastoma treated with pemigatinib: A case report and review of the literature. Neurooncol Adv. 2024 Jul 8;6(1):vdae116. doi: 10.1093/noajnl/vdae116. Erratum for: Neurooncol Adv. 2024 May 14;6(1):vdae072. doi: 10.1093/noajnl/vdae072. PMID: 38978962; PMCID: PMC11229027. 6: Long G, Wang D, Tang J, Hu K, Zhou L. USP8 promotes the tumorigenesis of intrahepatic cholangiocarcinoma via stabilizing OGT. Cancer Cell Int. 2024 Jul 7;24(1):238. doi: 10.1186/s12935-024-03370-w. PMID: 38973004; PMCID: PMC11229306. 7: Shinomiya R, Sato Y, Yoshimoto T, Kawaguchi T, Hirao A, Okamoto K, Kawano Y, Sogabe M, Miyamoto H, Takayama T. A case of treatment-resistant advanced gastric cancer with FGFR2 gene alteration successfully treated with pemigatinib. Int Cancer Conf J. 2024 Mar 9;13(3):240-244. doi: 10.1007/s13691-024-00669-3. PMID: 38962030; PMCID: PMC11217231. 8: Darwish IA, Alzoman NZ, Alsalhi MS. A green and highly sensitive microwell spectrofluorimetric method with high throughput for the determination of pemigatinib based on dual fluorescence enhancement by photoinduced electron transfer blocking and micellization: Application to the analysis of tablets, content uniformity testing, and human plasma. Luminescence. 2024 Jun;39(6):e4813. doi: 10.1002/bio.4813. PMID: 38922756. 9: Liu YT, Chen YH, Chang CH, Liang HT. Recurrent fibroblast growth factor receptor3 fusion glioblastoma treated with pemigatinib: A case report and review of the literature. Neurooncol Adv. 2024 May 14;6(1):vdae072. doi: 10.1093/noajnl/vdae072. Erratum in: Neurooncol Adv. 2024 Jul 08;6(1):vdae116. doi: 10.1093/noajnl/vdae116. PMID: 38845691; PMCID: PMC11154143. 10: Vogel A, Sahai V, Hollebecque A, Vaccaro GM, Melisi D, Al Rajabi RM, Paulson AS, Borad MJ, Gallinson D, Murphy AG, Oh DY, Dotan E, Catenacci DV, Van Cutsem E, Lihou CF, Zhen H, Veronese ML, Abou-Alfa GK. An open-label study of pemigatinib in cholangiocarcinoma: final results from FIGHT-202. ESMO Open. 2024 Jun;9(6):103488. doi: 10.1016/j.esmoop.2024.103488. Epub 2024 Jun 4. PMID: 38838500; PMCID: PMC11190465. 11: Ito Y, Yamada D, Kobayashi S, Sasaki K, Iwagami Y, Tomimaru Y, Asaoka T, Noda T, Takahashi H, Shimizu J, Doki Y, Eguchi H. The combination of gemcitabine plus an anti-FGFR inhibitor can have a synergistic antitumor effect on FGF- activating cholangiocarcinoma. Cancer Lett. 2024 Jul 28;595:216997. doi: 10.1016/j.canlet.2024.216997. Epub 2024 May 25. PMID: 38801887. 12: Rodón J, Damian S, Furqan M, García-Donas J, Imai H, Italiano A, Spanggaard I, Ueno M, Yokota T, Veronese ML, Oliveira N, Li X, Gilmartin A, Schaffer M, Goyal L. Publisher Correction: Pemigatinib in previously treated solid tumors with activating FGFR1-FGFR3 alterations: phase 2 FIGHT-207 basket trial. Nat Med. 2024 Aug;30(8):2377. doi: 10.1038/s41591-024-03072-w. Erratum for: Nat Med. 2024 Jun;30(6):1645-1654. doi: 10.1038/s41591-024-02934-7. PMID: 38789647. 13: Rodón J, Damian S, Furqan M, García-Donas J, Imai H, Italiano A, Spanggaard I, Ueno M, Yokota T, Veronese ML, Oliveira N, Li X, Gilmartin A, Schaffer M, Goyal L. Pemigatinib in previously treated solid tumors with activating FGFR1-FGFR3 alterations: phase 2 FIGHT-207 basket trial. Nat Med. 2024 Jun;30(6):1645-1654. doi: 10.1038/s41591-024-02934-7. Epub 2024 May 6. Erratum in: Nat Med. 2024 May 24. doi: 10.1038/s41591-024-03072-w. PMID: 38710951; PMCID: PMC11186762. 14: Kodali S, Connor AA, Brombosz EW, Ghobrial RM. Update on the Screening, Diagnosis, and Management of Cholangiocarcinoma. Gastroenterol Hepatol (N Y). 2024 Mar;20(3):151-158. PMID: 38680168; PMCID: PMC11047158. 15: Gilbert TM, Randle L, Quinn M, McGreevy O, O'leary L, Young R, Diaz-Neito R, Jones RP, Greenhalf B, Goldring C, Fenwick S, Malik H, Palmer DH. Molecular biology of cholangiocarcinoma and its implications for targeted therapy in patient management. Eur J Surg Oncol. 2024 Apr 17:108352. doi: 10.1016/j.ejso.2024.108352. Epub ahead of print. PMID: 38653586. 16: Jain NK, Tailang M, Thangavel N, Makeen HA, Albratty M, Najmi A, Alhazmi HA, Zoghebi K, Alagusundaram M, Jain HK, Chandrasekaran B. A comprehensive overview of selective and novel fibroblast growth factor receptor inhibitors as a potential anticancer modality. Acta Pharm. 2024 Mar 30;74(1):1-36. doi: 10.2478/acph-2024-0005. PMID: 38554385. 17: Zhao D, Long X, Wang J. Adverse events with pemigatinib in the real world: a pharmacovigilance study based on the FDA Adverse Event Reporting System. Expert Opin Drug Saf. 2024 May;23(5):599-605. doi: 10.1080/14740338.2024.2338250. Epub 2024 Apr 1. PMID: 38553867. 18: Shomali W, Gotlib J. World Health Organization and International Consensus Classification of eosinophilic disorders: 2024 update on diagnosis, risk stratification, and management. Am J Hematol. 2024 May;99(5):946-968. doi: 10.1002/ajh.27287. Epub 2024 Mar 29. PMID: 38551368. 19: Adashek JJ, Kato S, Sicklick JK, Lippman SM, Kurzrock R. If it's a target, it's a pan-cancer target: Tissue is not the issue. Cancer Treat Rev. 2024 Apr;125:102721. doi: 10.1016/j.ctrv.2024.102721. Epub 2024 Mar 21. PMID: 38522181; PMCID: PMC11093268. 20: Chandana SR, Frisch A, Mendoza S, Sinniah RS, Crysler O, Banga R, Perkins DE. Management and mechanism of calciphylaxis in a patient treated with the FGFR inhibitor pemigatinib-a case report. J Gastrointest Oncol. 2024 Feb 29;15(1):478-484. doi: 10.21037/jgo-23-139. Epub 2024 Feb 1. PMID: 38482230; PMCID: PMC10932651.