EVOCALCET

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C24H26N2O2
Molecular Weight	374.4754
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C[C@@H](N[C@H]1CCN(C1)C2=CC=C(CC(O)=O)C=C2)C3=C4C=CC=CC4=CC=C3

InChI

InChIKey=RZNUIYPHQFXBAN-XLIONFOSSA-N

InChI=1S/C24H26N2O2/c1-17(22-8-4-6-19-5-2-3-7-23(19)22)25-20-13-14-26(16-20)21-11-9-18(10-12-21)15-24(27)28/h2-12,17,20,25H,13-16H2,1H3,(H,27,28)/t17-,20+/m1/s1

HIDE SMILES / InChI

Molecular Formula	C24H26N2O2
Molecular Weight	374.4754
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/29724589 | https://www.kyowa-kirin.com/news_releases/2018/pdf/e20180522_01.pdf | https://www.ncbi.nlm.nih.gov/pubmed/29614098

Evocalcet (MT-4580, KHK7580) is an allosteric calcium-sensing receptor agonist. Evocalcet directly acts on calcium receptors on parathyroid cells to suppress synthesis and secretion of parathyroid hormone (PTH), and it consequently decreases serum PTH and serum calcium. ORKEDIA® TABLETS (generic name: evocalcet, code name: KHK7580) has been listed on the National Health Insurance (NHI) Drug Price List and launched for the treatment of secondary hyperparathyroidism in patients on maintenance dialysis in Japan.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Extracellular calcium-sensing receptor 1 Target ID: P41180 Gene ID: 846.0 Gene Symbol: CASR Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/29724589	Agonist 2752		93.0 nM [EC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Secondary hyperparathyroidism 9 Sources: https://www.kyowa-kirin.com/news_releases/2018/pdf/e20180522_01.pdf	Primary		Approved 8583	ORKEDIA Approved Use Secondary hyperparathyroidism in patients on maintenance dialysis. Launch Date 2018

C_max

Value	Dose	Analyte	Population
59 ng/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/30168004/	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	EVOCALCET plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
376 ng/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/30168004/	6 mg single, oral dose: 6 mg route of administration: Oral experiment type: SINGLE co-administered:	EVOCALCET plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
867 ng/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/30168004/	12 mg single, oral dose: 12 mg route of administration: Oral experiment type: SINGLE co-administered:	EVOCALCET plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1400 ng/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/30168004/	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	EVOCALCET plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
394 ng/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/30168004/	6 mg 1 times / day multiple, oral dose: 6 mg route of administration: Oral experiment type: MULTIPLE co-administered:	EVOCALCET plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
1050 ng/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/30168004/	12 mg 1 times / day multiple, oral dose: 12 mg route of administration: Oral experiment type: MULTIPLE co-administered:	EVOCALCET plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
61.9 ng/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/30254496/	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	EVOCALCET plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
210 ng/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/30254496/	4 mg single, oral dose: 4 mg route of administration: Oral experiment type: SINGLE co-administered:	EVOCALCET plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
706 ng/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/30254496/	12 mg single, oral dose: 12 mg route of administration: Oral experiment type: SINGLE co-administered:	EVOCALCET plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED

AUC

Value	Dose	Analyte	Population
601.6 ng × h/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/30168004/	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	EVOCALCET plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
4038.5 ng × h/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/30168004/	6 mg single, oral dose: 6 mg route of administration: Oral experiment type: SINGLE co-administered:	EVOCALCET plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
8855.8 ng × h/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/30168004/	12 mg single, oral dose: 12 mg route of administration: Oral experiment type: SINGLE co-administered:	EVOCALCET plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
15307.4 ng × h/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/30168004/	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	EVOCALCET plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
3860.6 ng × h/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/30168004/	6 mg 1 times / day multiple, oral dose: 6 mg route of administration: Oral experiment type: MULTIPLE co-administered:	EVOCALCET plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
10836.3 ng × h/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/30168004/	12 mg 1 times / day multiple, oral dose: 12 mg route of administration: Oral experiment type: MULTIPLE co-administered:	EVOCALCET plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
1288.5 ng × h/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/30254496/	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	EVOCALCET plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
5267.8 ng × h/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/30254496/	4 mg single, oral dose: 4 mg route of administration: Oral experiment type: SINGLE co-administered:	EVOCALCET plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
14680.4 ng × h/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/30254496/	12 mg single, oral dose: 12 mg route of administration: Oral experiment type: SINGLE co-administered:	EVOCALCET plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED

T_1/2

Value	Dose	Analyte	Population
19.77 h CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/30168004/	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	EVOCALCET plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
14.76 h CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/30168004/	6 mg single, oral dose: 6 mg route of administration: Oral experiment type: SINGLE co-administered:	EVOCALCET plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
12.98 h CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/30168004/	12 mg single, oral dose: 12 mg route of administration: Oral experiment type: SINGLE co-administered:	EVOCALCET plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
18.89 h CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/30168004/	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	EVOCALCET plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
18.5 h CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/30168004/	6 mg 1 times / day multiple, oral dose: 6 mg route of administration: Oral experiment type: MULTIPLE co-administered:	EVOCALCET plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
16.3 h CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/30168004/	12 mg 1 times / day multiple, oral dose: 12 mg route of administration: Oral experiment type: MULTIPLE co-administered:	EVOCALCET plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
20.9 h CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/30254496/	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	EVOCALCET plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
22.4 h CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/30254496/	4 mg single, oral dose: 4 mg route of administration: Oral experiment type: SINGLE co-administered:	EVOCALCET plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
22.5 h CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/30254496/	12 mg single, oral dose: 12 mg route of administration: Oral experiment type: SINGLE co-administered:	EVOCALCET plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED

Doses

Dose	Population	Adverse events
2 mg 1 times / day multiple, oral Recommended Dose: 2 mg, 1 times / day Route: oral Route: multiple Dose: 2 mg, 1 times / day Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_A100_1.pdf#page=36	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_A100_1.pdf#page=36	Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_A100_1.pdf#page=36
4 mg 1 times / day multiple, oral Recommended Dose: 4 mg, 1 times / day Route: oral Route: multiple Dose: 4 mg, 1 times / day Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_A100_1.pdf#page=30	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_A100_1.pdf#page=30	Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_A100_1.pdf#page=30
12 mg 1 times / day multiple, oral Studied dose Dose: 12 mg, 1 times / day Route: oral Route: multiple Dose: 12 mg, 1 times / day Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_A100_1.pdf#page=28	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M Food Status: FED Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_A100_1.pdf#page=28	Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_A100_1.pdf#page=28
12 mg 1 times / day multiple, oral Studied dose Dose: 12 mg, 1 times / day Route: oral Route: multiple Dose: 12 mg, 1 times / day Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_A100_1.pdf#page=41	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_A100_1.pdf#page=41	Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_A100_1.pdf#page=41
12 mg 1 times / day multiple, oral Studied dose Dose: 12 mg, 1 times / day Route: oral Route: multiple Dose: 12 mg, 1 times / day Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_A100_1.pdf#page=43	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_A100_1.pdf#page=43	Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_A100_1.pdf#page=43
8 mg 1 times / day multiple, oral Studied dose Dose: 8 mg, 1 times / day Route: oral Route: multiple Dose: 8 mg, 1 times / day Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_A100_1.pdf#page=38	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_A100_1.pdf#page=38	Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_A100_1.pdf#page=38

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946 inducer 1087	substrate 1193 inducer 440 inhibitor 2438	substrate 1388 inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2A6 879 CYP1A2 2153 P-gp 1741 OATP1B1 1079 OAT1 725 OATP1B3 961 CYP3A 227 CYP2C19 2057 CYP2E1 1060 OAT3 747 OCT2 779 MATE1 415 BCRP 910 MATE2-K 77 CYP2C8 1057 CYP2B6 926	CYP1A2 1197 CYP2C8 810 UGT1A3 470 CYP2C19 1119 UGT1A1 479 UGT1A9 423 UGT1A10 331 CYP2B6 776 UGT2B4 278 UGT2B7 456 UGT2B10 131 UGT1A7 249 UGT1A6 343 UGT2B15 236 CYP2E1 729 UGT1A4 399 UGT2B17 237 UGT1A8 323 OATP1B3 435 BCRP 697 P-gp 2052 OATP1B1 503	CYP1A2 832 CYP2C19 329 CYP2B6 669 CYP2C8 198

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP2C19 2141	inducer 1966 Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_I100_2.pdf Page: 29 \| 79	inconclusive
OATP1B3 970	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_A100_1.pdf Page: 27.0	no [IC50 11.2 uM]
MATE1 416	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_A100_1.pdf Page: 27.0	no [IC50 >10 uM]
MATE2-K 77	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_A100_1.pdf Page: 27.0	no [IC50 >10 uM]
OAT1 730	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_A100_1.pdf Page: 27.0	no [IC50 >10 uM]
OAT3 749	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_A100_1.pdf Page: 27.0	no [IC50 >10 uM]
OCT2 782	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_A100_1.pdf Page: 27.0	no [IC50 >10 uM]
CYP1A2 2333	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_A100_1.pdf Page: 27.0	no
CYP2A6 911	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_A100_1.pdf Page: 27.0	no
CYP2B6 1160	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_A100_1.pdf Page: 27.0	no
CYP2C19 2141	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_A100_1.pdf Page: 27.0	no
CYP2C8 1117	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_A100_1.pdf Page: 27.0	no
CYP2C9 2497	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_A100_1.pdf Page: 27.0	no
CYP2E1 1146	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_A100_1.pdf Page: 27.0	no
OATP1B1 1095	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_A100_1.pdf Page: 27.0	weak [IC50 11.2 uM]
P-gp 1932	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_A100_1.pdf Page: 27.0	weak [IC50 53.1 uM]
BCRP 985	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_A100_1.pdf Page: 27.0	weak [IC50 >50 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_A100_1.pdf Page: 27.0	weak [IC50 >50 uM]
CYP3A 317	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_A100_1.pdf Page: 27.0	weak
CYP1A2 2333	inducer 1966 Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_I100_2.pdf \| https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_A100_1.pdf#page=33 Page: 29 \| 78 \| 80	yes	no (co-administration study) Comment: Evocalcet did not significantly change theophylline Cmax and AUCt Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_I100_2.pdf \| https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_A100_1.pdf#page=33 Page: 29 \| 78 \| 80
CYP2B6 1160	inducer 1966 Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_I100_2.pdf \| https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_A100_1.pdf#page=33 Page: 29 \| 78 \| 80	yes	no (co-administration study) Comment: Evocalcet did not significantly change efavirenz Cmax and AUCt Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_I100_2.pdf \| https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_A100_1.pdf#page=33 Page: 29 \| 78 \| 80
CYP2C8 1117	inducer 1966 Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_I100_2.pdf \| https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_A100_1.pdf#page=33 Page: 29 \| 78	yes	no (co-administration study) Comment: Evocalcet did not significantly change repaglinide Cmax and AUCt Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_I100_2.pdf \| https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_A100_1.pdf#page=33 Page: 29 \| 78
CYP2C9 2497	inducer 1966 Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_I100_2.pdf \| https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_A100_1.pdf#page=33 Page: 29 \| 79	yes	no (co-administration study) Comment: Evocalcet did not significantly change diclofenac Cmax and AUCt Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_I100_2.pdf \| https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_A100_1.pdf#page=33 Page: 29 \| 79
CYP3A4 2633	inducer 1966 Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_I100_2.pdf \| https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_A100_1.pdf#page=33 Page: 29 \| 79 \| 80	yes	no (co-administration study) Comment: Evocalcet did not significantly change tadalafil Cmax and AUCt Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_I100_2.pdf \| https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_A100_1.pdf#page=33 Page: 29 \| 79 \| 80

Drug as victim

Target	Modality	Activity
BCRP 697	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_A100_1.pdf Page: 27.0	no
CYP1A2 1197	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_I100_2.pdf Page: 29.0	no
CYP2B6 776	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_I100_2.pdf Page: 29.0	no
CYP2C19 1119	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_I100_2.pdf Page: 29.0	no
CYP2C8 810	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_I100_2.pdf Page: 29.0	no
CYP2C9 1193	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_I100_2.pdf Page: 29.0	no
CYP2E1 729	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_I100_2.pdf Page: 29.0	no
OATP1B1 503	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_A100_1.pdf Page: 27.0	no
OATP1B3 435	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_A100_1.pdf Page: 27.0	no
P-gp 2052	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_A100_1.pdf Page: 27.0	no
UGT1A10 331	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_I100_2.pdf Page: 29.0	no
UGT1A4 399	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_I100_2.pdf Page: 29.0	no
UGT1A6 343	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_I100_2.pdf Page: 29.0	no
UGT1A7 249	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_I100_2.pdf Page: 29.0	no
UGT1A8 323	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_I100_2.pdf Page: 29.0	no
UGT1A9 423	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_I100_2.pdf Page: 29.0	no
UGT2B10 131	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_I100_2.pdf Page: 29.0	no
UGT2B15 236	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_I100_2.pdf Page: 29.0	no
UGT2B17 237	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_I100_2.pdf Page: 29.0	no
UGT2B4 278	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_I100_2.pdf Page: 29.0	no
UGT2B7 456	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_I100_2.pdf Page: 29.0	no
UGT1A1 479	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_I100_2.pdf Page: 29.0	weak
UGT1A3 470	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_I100_2.pdf Page: 29.0	weak
CYP2D6 1388	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_I100_2.pdf Page: 29.0	yes
CYP3A4 1946	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_I100_2.pdf Page: 29.0	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.pmda.go.jp/drugs/2018/P20180413003/230124000_23000AMX00465_A100_1.pdf Page: 10.0

PubMed

Title	Date	PubMed
Long-Term Efficacy and Safety of Evocalcet in Japanese Patients with Secondary Hyperparathyroidism Receiving Hemodialysis.	2019-04-23	31015494
Discovery of evocalcet, a next-generation calcium-sensing receptor agonist for the treatment of hyperparathyroidism.	2018-06-15	29724589
A novel calcimimetic agent, evocalcet (MT-4580/KHK7580), suppresses the parathyroid cell function with little effect on the gastrointestinal tract or CYP isozymes in vivo and in vitro.	2018	29614098

Patents

Sample Use Guides

In Vivo Use Guide

In general, for adults, start by taking 1 tablet (1 mg of the active ingredient) at a time, once daily, then the dosage may be adjusted between 1 to 8 tablets (1 to 8 mg) by observing PTH and serum calcium level. Depending on your condition, the dosage may start from 2 tablets (2 mg) at a time, once daily. The maximum daily dose is limited to 12 tablets (12 mg). Dose should be increased by 1 tablet (1 mg) at a time, at intervals of at least two weeks. Strictly follow the instructions.

Route of Administration: Oral

Substance Class	Chemical Created by `admin` on `Mon Mar 31 23:29:49 GMT 2025` Edited by `admin` on `Mon Mar 31 23:29:49 GMT 2025`
Record UNII	E58MLH082P
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

EVOCALCET

Official Name

English

evocalcet [INN]

Preferred Name

English

Evocalcet [WHO-DD]

Common Name

English

BENZENEACETIC ACID, 4-((3S)-3-(((1R)-1-(1-NAPHTHALENYL)ETHYL)AMINO)-1-PYRROLIDINYL)-

Systematic Name

English

MT-4580

Code

English

KHK7580

Code

English

EVOCALCET [JAN]

Common Name

English

KHK-7580

Code

English

EVOCALCET [MI]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C2136