소니데기브

Sonidegib
소니데기브
Sonidegib.svg
임상자료
상명오돔조
기타 이름LDE225, 에리스모데기브
AHFS/Drugs.com모노그래프
메드라인플러스a615034
라이센스 데이터
임신
범주
  • 콘트라인 (X)
경로:
행정		입으로(캡슐)
마약류항소성제
ATC 코드
법적현황
법적현황
  • US: ℞ 전용
  • EU: Rx 전용
  • 일반: ℞ (처방에만 해당)
약동학 데이터
생체이용가능성<10%
단백질 결합>97%
신진대사간(CYP3A)
제거 반감기~28일
배설대변(~70%), 소변(30%)[2]
식별자
  • N-[6-[(2S,6R)-2,6-디메틸모르폴린-4-yl]피리딘-3-yl]-2-메틸-3-[4-(트리플루오메트호xy)페닐페닐페닐아미드
CAS 번호
펍켐 CID
드러그뱅크
켐스파이더
유니
케그
체비
켐벨
CompTox 대시보드 (EPA)
화학 및 물리적 데이터
공식C26H26F3N3O3
어금질량485.507 g·1998−1
3D 모델(JSmol)
  • C[C@@H]1CN(C[C@@H](O1)C)C2=NC=C(C=C2)NC(=O)C3=CC=CC(=C3C)C4=CC=C(C=C4)OC(F)(F)f
  • InChI=1S/C26H26F3N3O3/c1-16-14-32(15-17(2)34-16)24-12-9-20(13-30-24)31-25(33)23-6-4-5-22(18(23)3)19-7-10-21(11-8-19)35-26(27,28)29/h4-13,16-17H,14-15H2,1-3H3,(H,31,33)/t16-,17+
  • 키:VZJRRRQSPEMTK-CALCHBBNSA-N

오돔조라는 상표명으로 판매되는 소니데기브(INN)는 암 치료에 쓰이는 약이다.[2]

소니데기브는 고슴도치 신호 경로 억제제다.[3][4]

승인 및 표시

2015년[5][6][7][8] 미국과 유럽연합(EU)에서 의료용으로 승인됐다.

수술이나 방사선 치료 후 재발한 국소적으로 발달한 기저세포암을 가진 성인이나, 수술이나 방사선 치료의 대상이 아닌 성인을 치료하기 위한 것이다.[2]

약리학

소니데기브는 입으로 투여한다.일반적인 부작용으로는 근육 경련, 탈모, 피로, 복통, 메스꺼움, 두통, 체중 감량이 있다.[2]

소니데기브는 고슴도치 경로의 활성화를 억제하기 위해 매끄럽게 결합하고 억제한다.소니데기브는 주로 CYP3A에 의해 대사되며 간으로 제거된다.[2]

개발

다음에 대한 잠재적 치료법으로서 조사되었다.

그것은 체외 및 체내 흑색종에 대해 상당한 효능을 보였다.[27]쥐의 췌장암 모델에서도 효능을 입증했다.[28]

참조

  1. ^ https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/205266s004lbl.pdf[bare URL PDF]
  2. ^ a b c d e "Odomzo- sonidegib capsule". DailyMed. 29 May 2019. Retrieved 9 June 2020.
  3. ^ "LDE225 - PubChem". PubChem. National Institutes of Health. Retrieved 16 February 2014.
  4. ^ Pan S, Wu X, Jiang J, Gao W, Wan Y, Cheng D, et al. (June 2010). "Discovery of NVP-LDE225, a Potent and Selective Smoothened Antagonist". ACS Medicinal Chemistry Letters. 1 (3): 130–4. doi:10.1021/ml1000307. PMC 4007689. PMID 24900187.
  5. ^ "FDA approves new treatment for most common form of advanced skin cancer". www.fda.gov. Retrieved 2015-07-24.[데드링크]
  6. ^ "Odomzo sonidegib Capsules". U.S. Food and Drug Administration (FDA). 28 August 2015. Retrieved 9 June 2020.
  7. ^ "FDA approves Novartis's advanced skin cancer drug". Retrieved 2015-07-24.
  8. ^ "Odomzo". European Medicines Agency. 17 September 2018. Retrieved 9 June 2020.
  9. ^ "A Biomarker Study to Identify Predictive Signatures of Response to LDE225 (Hedgehog Inhibitor) In Patients With Resectable Pancreatic Cancer". ClinicalTrials.gov. National Institutes of Health. 13 February 2014. Retrieved 16 February 2014.
  10. ^ "Gemcitabine + Nab-paclitaxel With LDE-225 (Hedgehog Inhibitor) as Neoadjuvant Therapy for Pancreatic Adenocarcinoma". ClinicalTrials.gov. National Institutes of Health. 13 February 2014. Retrieved 16 February 2014.
  11. ^ "Dose-escalation, and Safety Study of LDE225 and Gemcitabine in Locally Advanced or Metastatic Pancreatic Cancer Patients". ClinicalTrials.gov. National Institutes of Health. 13 February 2014. Retrieved 16 February 2014.
  12. ^ "A Pilot Study of a Hedgehog Pathway Inhibitor (LDE-225) in Surgically Resectable Pancreas Cancer". ClinicalTrials.gov. National Institutes of Health. 13 February 2014. Retrieved 16 February 2014.
  13. ^ "Study With LDE225 in Combination With Docetaxel in Triple Negative (TN) Advanced Breast Cancer (ABC) Patients (EDALINE)". ClinicalTrials.gov. National Institutes of Health. 13 February 2014.
  14. ^ "LDE225 in Treating Patients With Stage II-III Estrogen Receptor- and HER2-Negative Breast Cancer". ClinicalTrials.gov. National Institutes of Health. 13 February 2014. Retrieved 16 February 2014.
  15. ^ "A Phase II Study of Efficacy and Safety in Patients With Locally Advanced or Metastatic Basal Cell Carcinoma (BOLT)". ClinicalTrials.gov. National Institutes of Health. 13 February 2014. Retrieved 16 February 2014.
  16. ^ "To Evaluate the Safety, Local Tolerability, PK and PD of LDE225 on Sporadic Superficial and Nodular Skin Basal Cell Carcinomas(sBCC)". ClinicalTrials.gov. National Institutes of Health. 13 February 2014. Retrieved 16 February 2014.
  17. ^ "A Trial to Evaluate the Safety, Local Tolerability, Pharmacokinetics and Pharmacodynamics of LDE225 on Skin Basal Cell Carcinomas in Gorlin Syndrome Patients". ClinicalTrials.gov. National Institutes of Health. 13 February 2014. Retrieved 16 February 2014.
  18. ^ "Combination of the Hedgehog Inhibitor, LDE225, With Etoposide and Cisplatin in the First-Line Treatment of Patients With Extensive Stage Small Cell Lung Cancer (ES-SCLC)". ClinicalTrials.gov. National Institutes of Health. 13 February 2014. Retrieved 16 February 2014.
  19. ^ "A Phase III Study of Oral LDE225 Versus (vs) Temozolomide (TMZ) in Patients With Hedge-Hog (Hh)-Pathway Activated Relapsed Medulloblastoma (MB)". ClinicalTrials.gov. National Institutes of Health. 13 February 2014. Retrieved 16 February 2014.
  20. ^ "A Phase I Dose Finding and Safety Study of Oral LDE225 in Children and a Phase II Portion to Assess Preliminary Efficacy in Recurrent or Refractory MB". ClinicalTrials.gov. National Institutes of Health. 13 February 2014. Retrieved 16 February 2014.
  21. ^ "Phase Ib, Dose Escalation Study of Oral LDE225 in Combination With BKM120 in Patients With Advanced Solid Tumors". ClinicalTrials.gov. National Institutes of Health. 13 February 2014. Retrieved 16 February 2014.
  22. ^ "Dose Finding and Safety of Oral LDE225 in Patients With Advanced Solid Tumors". ClinicalTrials.gov. National Institutes of Health. 13 February 2014. Retrieved 16 February 2014.
  23. ^ "LDE225 and Paclitaxel in Solid Tumors". ClinicalTrials.gov. National Institutes of Health. 13 February 2014. Retrieved 16 February 2014.
  24. ^ "Study of Efficacy and Safety of LDE225 in Adult Patients With Relapsed/Refractory Acute Leukemia". ClinicalTrials.gov. National Institutes of Health. 13 February 2014. Retrieved 16 February 2014.
  25. ^ "Nilotinib and LDE225 in the Treatment of Chronic or Accelerated Phase Myeloid Leukemia in Patients Who Developed Resistance to Prior Therapy". ClinicalTrials.gov. National Institutes of Health. 13 February 2014. Retrieved 16 February 2014.
  26. ^ "A Phase Ib/II Dose-finding Study to Assess the Safety and Efficacy of LDE225 + INC424 in Patients With MF". ClinicalTrials.gov. National Institutes of Health. 13 February 2014. Retrieved 16 February 2014.
  27. ^ Jalili A, Mertz KD, Romanov J, Wagner C, Kalthoff F, Stuetz A, et al. (30 July 2013). "NVP-LDE225, a potent and selective SMOOTHENED antagonist reduces melanoma growth in vitro and in vivo". PLOS ONE. 8 (7): e69064. Bibcode:2013PLoSO...869064J. doi:10.1371/journal.pone.0069064. PMC 3728309. PMID 23935925.
  28. ^ Fendrich V, Wiese D, Waldmann J, Lauth M, Heverhagen AE, Rehm J, Bartsch DK (November 2011). "Hedgehog inhibition with the orally bioavailable Smo antagonist LDE225 represses tumor growth and prolongs survival in a transgenic mouse model of islet cell neoplasms". Annals of Surgery. 254 (5): 818–23, discussion 823. doi:10.1097/SLA.0b013e318236bc0f. PMID 22042473. S2CID 12947375.

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