기본 정보
- CAS
664334-36-5- 표준 SMILES
N=C(N)NCCC[C@H](NC(=O)[C@@H]1CSSC[C@H](NC(=O)[C@H](Cc2ccc3ccccc3c2)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)c2ccc(F)cc2)C(=O)N[C@@H](Cc2ccc(O)cc2)C(=O)N[C@@H](CCCNC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N2CCC[C@H]2C(=O)N[C@@H](Cc2ccc(O)cc2)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(N)=O)C(=O)N1)C(N)=O- InChIKey
JJVZSYKFCOBILL-KZGZZEQFSA-N- 분자식
- C97H144FN33O19S2
- 평균 분자량
- 2,159.5 g/mol
- 단동위원소 질량
- 2,158.07417
개요
Motixafortide is a heterodetic cyclic peptide that has antineoplastic activity. It is a CXC chemokine receptor 4 (CXCR4) antagonist with an IC50 value of 0.8 nM and is currently under clinical investigation for the treatment of hematological malignancies, solid tumors, and stem cell mobilization. It was granted orphan drug designation by the FDA for the treatment of pancreatic cancer in 2019. It has a role as a C-X-C chemokine receptor type 4 antagonist, an antineoplastic agent and an apoptosis inducer.
이름 및 식별자
- 우선 이름
- Motixafortide
- IUPAC
- (3S,6S,9S,12S,15R,20R,23S,26S,29S,32S)-3,6-bis(4-aminobutyl)-N-[(2S)-1-amino-5-carbamimidamido-1-oxopentan-2-yl]-15-[[(2S)-2-[[(2S)-5-carbamimidamido-2-[[(2S)-5-carbamimidamido-2-[(4-fluorobenzoyl)amino]pentanoyl]amino]pentanoyl]amino]-3-naphthalen-2-ylpropanoyl]amino]-26-(3-carbamimidamidopropyl)-9,23-bis[3-(carbamoylamino)propyl]-12,29-bis[(4-hydroxyphenyl)methyl]-2,5,8,11,14,22,25,28,31-nonaoxo-17,18-dithia-1,4,7,10,13,21,24,27,30-nonazabicyclo[30.3.0]pentatriacontane-20-carboxamide
- 영어명
- BL-8040
- 분자식
- C97H144FN33O19S2
- 분자량
- 2159.53
이름 및 동의어
MotixafortideBL-8040BKT1404F-benzoyl-TN14003664334-36-5motixafortidamotixafortidumTF14016BKT 140DA9G065962TF 14016BKT-140
이름 더 보기
Motixafortide (BL-8040, BKT140)BKT140, >99%BKT140 (BL-8040)Motixafortide(TFA)Motixafortide(BKT140)
TF-14016CHEBI:1455364F-BENZOYL-TN-14003BL 8040N-(4-FLUORO-BENZOYL)-L-ARGINYL-L-ARGINYL-(L-3-(NAPHTHYL)ALANYL)-L-CYSTEINYL-L-TYROSYL-L-CITRULLINYL-L-LYSYL-D-LYSYL-L-PROLYL-L-TYROSYL-L-ARGINYL-L-CITRULLINYL-L-CYSTEINYL-L-ARGININE AMIDE,CYCLIC (4-13)-DISULFIDERefChem:819543(3S,6S,9S,12S,15R,20R,23S,26S,29S,32S)-3,6-bis(4-aminobutyl)-N-((2S)-1-amino-5-carbamimidamido-1-oxopentan-2-yl)-15-(((2S)-2-(((2S)-5-carbamimidamido-2-(((2S)-5-carbamimidamido-2-((4-fluorobenzoyl)amino)pentanoyl)amino)pentanoyl)amino)-3-naphthalen-2-ylpropanoyl)amino)-26-(3-carbamimidamidopropyl)-9,23-bis(3-(carbamoylamino)propyl)-12,29-bis((4-hydroxyphenyl)methyl)-2,5,8,11,14,22,25,28,31-nonaoxo-17,18-dithia-1,4,7,10,13,21,24,27,30-nonazabicyclo(30.3.0)pentatriacontane-20-carboxamideMotixafortide [USAN]
데이터베이스 식별자
물성
구조 계산 물성
- XLogP
- -2.9
- 극성 표면적
- 943 Ų
- 수소 결합 공여자 수
- 34
- 수소 결합 수용자 수
- 28
- 회전 가능 결합 수
- 53
- 무거운 원자 수
- 152
- 형식 전하
- 0
- 복잡도
- 4,500
물리화학적 성질
- 밀도
- 1.52 · 1.52±0.1 g/cm3(Predicted)
- 저장 조건
- -20 °C · Store at -20°C
- 용해도
- 216 mg/mL · ≥216 mg/mL in DMSO; ≥2.61 mg/mL in EtOH with gentle warming and ultrasonic; ≥52.4 mg/mL in H2O
- 물리적 상태
- 결정성 고체
- 색상
- White to off-white
안전 및 규제
안전 정보는 참고용이며, 공급업체의 물질안전보건자료(SDS), 관련 법규 및 전문가 평가를 대체하지 않습니다.
안전 데이터
- 신호 어
- Warning
- 유해·위험 문구
- 암호 유해·위험 문구 위험 등급 범주 신호 어 그림 문자 P- 코드 H302
화학 및 산업
약리 정보
ATC Code
L - Antineoplastic and immunomodulating agents
QL - Antineoplastic and immunomodulating agents
Protein BindingMotixafortide is extensively (>99%) bound to human plasma proteins, although the specific protein(s) to which it may bind are unclear.
Pharmacodynamics
_In vitro_ studies have shown motixafortide to have an IC<sub>50</sub> towards CXCR4 of 0.42 – 4.5 nM, with a binding affinity and dissociation rate that allows receptor occupancy to be maintained >72 hours. In healthy volunteers administered motixafortide monotherapy, CD34+ cell counts increased over time and reached maximal levels at 16 hours postdose. In the GENESIS study, motixafortide in combination with filgrastim mobilized significantly greater CD34+ HSPC numbers within two apheresis procedures compared to filgrastim with placebo, while preferentially mobilizing increased numbers of immunophenotypically and transcriptionally primitive HSPCs.
Mechanism of Action
Motixafortide is an inhibitor of C-X-C Motif Chemokine Receptor 4 (CXCR4) that blocks the binding of its ligand, stromal-derived factor-1α (SDF-1α)/C-X-C Motif Chemokine Ligand 12 (CXCL12). Both CXCR4 and SDF-1α play a role in the trafficking of hematopoietic stem cells to the bone marrow compartment, with CXCR4 helping to anchor stem cells to the marrow matrix (via SDF-1α or the induction of other adhesion molecules). The inhibition of CXCR4 thus results in elevations in circulating hematopoietic stem and progenitor cells into the peripheral circulation, facilitating their collection for the purposes of autologous transplantation.
Biological Half-LifeThe effective half-life of motixafortide in human plasma is approximately 2 hours.
Metabolism/MetabolitesMotixafortide is broken down via non-specific catabolic processes to smaller peptides and amino acids.
Absorption, Distribution and Excretion
Following subcutaneous injection, motixafortide Tmax ranged from 0.25 to 1.17 hours.
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