| Target General Information |
| Target ID |
T11211
|
| Target Name |
Androgen receptor (AR) |
| Gene Name |
AR |
| Species |
Homo sapiens |
| UniProt ID |
ANDR_HUMAN |
| Sequence |
MEVQLGLGRVYPRPPSKTYRGAFQNLFQSVREVIQNPGPRHPEAASAAPPGASLLLLQQQ
QQQQQQQQQQQQQQQQQQQQETSPRQQQQQQGEDGSPQAHRRGPTGYLVLDEEQQPSQPQ
SALECHPERGCVPEPGAAVAASKGLPQQLPAPPDEDDSAAPSTLSLLGPTFPGLSSCSAD
LKDILSEASTMQLLQQQQQEAVSEGSSSGRAREASGAPTSSKDNYLGGTSTISDNAKELC
KAVSVSMGLGVEALEHLSPGEQLRGDCMYAPLLGVPPAVRPTPCAPLAECKGSLLDDSAG
KSTEDTAEYSPFKGGYTKGLEGESLGCSGSAAAGSSGTLELPSTLSLYKSGALDEAAAYQ
SRDYYNFPLALAGPPPPPPPPHPHARIKLENPLDYGSAWAAAAAQCRYGDLASLHGAGAA
GPGSGSPSAAASSSWHTLFTAEEGQLYGPCGGGGGGGGGGGGGGGGGGGGGGGEAGAVAP
YGYTRPPQGLAGQESDFTAPDVWYPGGMVSRVPYPSPTCVKSEMGPWMDSYSGPYGDMRL
ETARDHVLPIDYYFPPQKTCLICGDEASGCHYGALTCGSCKVFFKRAAEGKQKYLCASRN
DCTIDKFRRKNCPSCRLRKCYEAGMTLGARKLKKLGNLKLQEEGEASSTTSPTEETTQKL
TVSHIEGYECQPIFLNVLEAIEPGVVCAGHDNNQPDSFAALLSSLNELGERQLVHVVKWA
KALPGFRNLHVDDQMAVIQYSWMGLMVFAMGWRSFTNVNSRMLYFAPDLVFNEYRMHKSR
MYSQCVRMRHLSQEFGWLQITPQEFLCMKALLLFSIIPVDGLKNQKFFDELRMNYIKELD
RIIACKRKNPTSCSRRFYQLTKLLDSVQPIARELHQFTFDLLIKSHMVSVDFPEMMAEII
SVQVPKILSGKVKPIYFHTQ [Homo sapiens]
|
| Drug and Corresponding Resistance Mutations |
| Mutation Info |
Missense: F876L |
| Drugs |
| Drug Name |
Enzalutamide |
Drug Info
|
[4] |
| Targeted Disease |
Prostate Cancer |
|
|
|
| Mutation Info |
Missense: F877L |
| Drugs |
| Drug Name |
Enzalutamide |
Drug Info
|
[1], [2] |
| Targeted Disease |
Prostate Cancer |
|
| Drug Name |
Arn-509 |
Drug Info
|
[1] |
| Targeted Disease |
Prostate Cancer |
|
| Mutation Info |
Missense: L702H |
| Drugs |
| Drug Name |
Abiraterone |
Drug Info
|
[11] |
| Targeted Disease |
Prostate Cancer |
| Mutation Prevalence |
3 out of 59 patients |
|
| Mutation Info |
Missense: Q641* |
| Drugs |
| Drug Name |
Flutamide |
Drug Info
|
[7] |
| Targeted Disease |
Prostate Cancer |
|
| Mutation Info |
Missense: T878A |
| Drugs |
| Drug Name |
Enzalutamide |
Drug Info
|
[2], [3] |
| Targeted Disease |
Prostate Cancer |
| Mutation Prevalence |
2 out of 62 patients |
|
| Drug Name |
Flutamide |
Drug Info
|
[6], [7], [8] |
| Targeted Disease |
Prostate Cancer |
|
| Drug Name |
Abiraterone |
Drug Info
|
[11] |
| Targeted Disease |
Prostate Cancer |
| Mutation Prevalence |
4 out of 59 patients |
|
| Drug Name |
Androgen |
Drug Info
|
[2] |
| Targeted Disease |
Prostate Cancer |
| Mutation Prevalence |
2 out of 62 patients |
|
| Mutation Info |
Missense: T878S |
| Drugs |
| Drug Name |
Flutamide |
Drug Info
|
[10] |
| Targeted Disease |
Prostate Cancer |
| Mutation Prevalence |
1 out of 4 patients |
|
| Drug Name |
Abiraterone |
Drug Info
|
[11] |
| Targeted Disease |
Prostate Cancer |
|
| Mutation Info |
Missense: V716M |
| Drugs |
| Drug Name |
Flutamide |
Drug Info
|
[9] |
| Targeted Disease |
Prostate Cancer |
| Mutation Prevalence |
3 out of 28 patients |
|
| Drug Name |
Androgen |
Drug Info
|
[12] |
| Targeted Disease |
Prostate Cancer |
|
| Mutation Info |
Missense: W741C |
| Drugs |
| Drug Name |
Bicalutamide |
Drug Info
|
[5] |
| Targeted Disease |
Prostate Cancer |
|
| Mutation Info |
Missense: W741L |
| Drugs |
| Drug Name |
Bicalutamide |
Drug Info
|
[5] |
| Targeted Disease |
Prostate Cancer |
|
| References |
| REF 1 |
A clinically relevant androgen receptor mutation confers resistance to second-generation antiandrogens enzalutamide and ARN-509. Cancer Discov. 2013 Sep;3(9):1020-9.
|
| REF 2 |
Androgen Receptor Gene Aberrations in Circulating Cell-Free DNA: Biomarkers of Therapeutic Resistance in Castration-Resistant Prostate Cancer. Clin Cancer Res. 2015 May 15;21(10):2315-24.
|
| REF 3 |
Integrated Analysis of Multiple Biomarkers from Circulating Tumor Cells Enabled by Exclusion-Based Analyte Isolation. Clin Cancer Res. 2017 Feb;23(3):746-756.
|
| REF 4 |
An F876L mutation in androgen receptor confers genetic and phenotypic resistance to MDV3100 (enzalutamide).Cancer Discov.2013 Sep;3(9):1030-43.
|
| REF 5 |
Progress in antiandrogen design targeting hormone binding pocket to circumvent mutation based resistance. Front Pharmacol. 2015 Mar 24;6:57.
|
| REF 6 |
Androgen receptor mutations in androgen-independent prostate cancer: Cancer and Leukemia Group B Study 9663. J Clin Oncol. 2003 Jul 15;21(14):2673-8.
|
| REF 7 |
Constitutive activation of the androgen receptor by a point mutation in the hinge region: a new mechanism for androgen-independent growth in prostate cancer. Int J Cancer. 2004 Jan 1;108(1):152-7.
|
| REF 8 |
A mutation in the ligand binding domain of the androgen receptor of human LNCaP cells affects steroid binding characteristics and response to anti-androgens. Biochem Biophys Res Commun. 1990 Dec 14;173(2):534-40.
|
| REF 9 |
Treatment-dependent androgen receptor mutations in prostate cancer exploit multiple mechanisms to evade therapy. Cancer Res. 2009 May 15;69(10):4434-42.
|
| REF 10 |
Mutation of the androgen-receptor gene in metastatic androgen-independent prostate cancer. N Engl J Med. 1995 May 25;332(21):1393-8.
|
| REF 11 |
Plasma AR and abiraterone-resistant prostate cancer. Sci Transl Med. 2015 Nov 4;7(312):312re10.
|
| REF 12 |
Mutant androgen receptor detected in an advanced-stage prostatic carcinoma is activated by adrenal androgens and progesterone. Mol Endocrinol. 1993 Dec;7(12):1541-50.
|
| REF 13 |
Discovery of ODM-201, a new-generation androgen receptor inhibitor targeting resistance mechanisms to androgen signaling-directed prostate cancer therapies. Sci Rep. 2015 Jul 3;5:12007.
|
