Fludarabine

2-fluoroadenine-9-β-d-arabinofuranoside · f-ara-a · Fludara · CS-1983 · Darabin · 2-F-ARAA · NSC 118218 · NSC-312887

https://huagongshe.com/ko/chemical/657237

식별자 및 물리적 특성

CAS No.	21679-14-1
분자식	C10H12FN5O4
평균 분자량	285.23 g/mol
단동위원소 질량	285.08733208 g/mol
SMILES	Nc1nc(F)nc2c1ncn2[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1O
InChIKey	HBUBKKRHXORPQB-FJFJXFQQSA-N
PubChem CID	657237
ChEMBL	CHEMBL1568
ChEBI	CHEBI:94701
EC No.	244-525-5
DTXSID	DTXSID4039657

화학 및 물리적 성질

XLogP	-0.6
극성 표면적	140
수소 결합 공여자 수	4
수소 결합 수용자 수	9
회전 가능 결합 수	2
무거운 원자 수	20
형식 전하	0
복잡도	367
의약품	Pharmaceuticals -> Listed in ZINC15Pharmaceuticals -> Antineoplastic and immunomodulating agents -> Antineoplastic agents
Color/Form	Crystals
용해도	Sparingly sol water, org solventsDMF: 20mg/mL, 투명, 희미한 노란색
Human Drugs	Breast FeedingLactationMilk, HumanAntineoplastic AgentsCytotoxic medicines
녹는점	260 °C265-268°C
Collision Cross Section	164.81 Å² [M+Na]+ [CCS Type: TWMethod: calibrated with polyalanine and drug standards]
끓는 점	747.3±70.0 °C(Predicted)
밀도	2.17±0.1 g/cm3(Predicted)
저장 조건	2-8°C
물리적 상태	가루
pKa(산도 계수)	13.05±0.70(Predicted)
색상	흰색에서 연한 노란색
용해도	DMF, DMSO, 메탄올 또는 에탄올에 용해됩니다. 물에 거의 녹지 않음
Merck	13,4152
BRN	1225932
안정성	제공된 대로 구매일로부터 1년 동안 안정적입니다. DMSO 용액은 -20°C에서 최대 3개월 동안 보관할 수 있습니다.
InChI	InChI=1/C10H12FN5O4/c11-10-14-7(12)4-8(15-10)16(2-13-4)9-6(19)5(18)3(1-17)20-9/h2-3,5-6,9,17-19H,1H2,(H2,12,14,15)/t3-,5-,6+,9-/s3
InChIKey	HBUBKKRHXORPQB-VOSPVXAENA-N
SMILES	C12N=C(N=C(N)C=1N=CN2[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1)F \|&1:10,11,13,15,r\|

화학적 성질

White Solid

안전 및 규제

Drug Induced Liver Injury
GHS 분류	WarningH302 (95.5%): Harmful if swallowed [Warning Acute toxicity, oral]P264, P270, P301+P317, P330, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 44 reports by companies from 6 notifications to the ECHA C&L Inventory.
Hazard Classes and Categories	Acute Tox. 4 (95.5%)
처리 방법	SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.
상호 작용	Fludarabine may raise the concentration of blood uric acid as part of a tumor lysis syndromedosage adjustment of antigout agents /allopurinol, colchicine, probenecid, sulfinpyrazone/ may be necessary to control hyperuricemia and goutallopurinol may be preferred to prevent or reverse fludarabine-induced hyperuricemia because of risk of uric acid nephropathy with uricosuric antigout agents.Leukopenic and/or thrombocytopenic effects of fludarabine may be increased with concurrent or recent therapy if these medications /blood dyscrasia causing medications/ cause the same effectsdosage adjustment of fludarabine, if necessary, should be based on blood counts.Additive bone marrow depression may occurdosage reduction may be required when two or more bone marrow depressants, including radiation, are used concurrently or consecutively.Concurrent use with fludarabine is not recommended because of a possible increased risk of fatal pulmonary toxicity. /Pentostatin/For more Interactions (Complete) data for FLUDARABINE (10 total), please visit the HSDB record page.
Hepatotoxicity	In clinical trials, serum enzymes elevations occurred in only a small proportion of patients treated with fludarabine for leukemia. The role of fludarabine as opposed to other antineoplastics used in antileukemic regimens was not always clear from these studies. Cases of clinically apparent liver injury due to fludarabine have been reported to occur, but few details were available and most patients were receiving other cancer chemotherapeutic agents.

용도

Fludarabine is not one of the most used drugs in pediatric oncology area. It is used in combination with other drugs to treat AML in children, mostly those who are receiving second-line therapy. It is commonly sold as 10 mg film-coated tablets and IV vial containing 50mg.

일반 설명

The drug is available as the phosphate salt in a 50-mg vialfor IV use. Fludarabine is used to treat chronic lymphocyticleukemia and non-Hodgkin’s lymphoma. The mechanism ofaction involves the triphosphate metabolite and its inhibitionof DNA chain elongation. The 2-fluoro group on the adeninering renders fludarabine resistant to breakdown byadenosine deaminase. The drug is rapidly dephosphorylatedto 2-fluoro-ara-adenosine (F-ara-A) after administration. Fara-A is taken into the cell and subsequently re-phosphorylatedto yield the triphosphate (F-ara-ATP), the active drugspecies. Resistance can occur via decreased expression ofthe activating enzymes and decreased drug transport.Fludarabine is orally bioavailable and is distributed throughoutthe body reaching high levels in liver, kidney, andspleen. The drug is metabolized to F-ara-A, which enterscells via the nucleoside transport system and is rephosphorylatedby deoxycytidine kinase to fludarabine monophosphateand finally fludarabine triphosphate, the activespecies. About 25% of F-ara-A is excreted unchanged inurine. Drug interactions include an increased incidence offatal pulmonary toxicity when fludarabine is used in combinationwith pentostatin. Additionally, fludarabine may potentiate the effects of several other anticancer drugs includingcytarabine, cyclophosphamide, and cisplatin.Toxicities include myelosuppression, immunosuppression,fever, nausea, and vomiting.