FINERENONE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C21H22N4O3
Molecular Weight	378.4244
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

CCOC1=NC=C(C)C2=C1[C@H](C3=CC=C(C=C3OC)C#N)C(C(N)=O)=C(C)N2

InChI

InChIKey=BTBHLEZXCOBLCY-QGZVFWFLSA-N

InChI=1S/C21H22N4O3/c1-5-28-21-18-17(14-7-6-13(9-22)8-15(14)27-4)16(20(23)26)12(3)25-19(18)11(2)10-24-21/h6-8,10,17,25H,5H2,1-4H3,(H2,23,26)/t17-/m1/s1

HIDE SMILES / InChI

Molecular Formula	C21H22N4O3
Molecular Weight	378.4244
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description

Finerenone (Kerendia®), a first-in-class, orally administered, selective, nonsteroidal mineralocorticoid receptor antagonist (MRA), is being developed by Bayer HealthCare Pharmaceuticals for the treatment of diabetic kidney disease (DKD) and heart failure (HF), including chronic HF (CHF). Finerenone blocks MR mediated sodium reabsorption and MR overactivation in both epithelial (e.g., kidney) and nonepithelial (e.g., heart, and blood vessels) tissues. MR overactivation is thought to contribute to fibrosis and inflammation. Finerenone has a high potency and selectivity for the MR and has no relevant affinity for androgen, progesterone, estrogen, and glucocorticoid receptors. Finerenone has been approved in the USA to reduce the risk of sustained estimated glomerular filtration rate (eGFR) decline, end stage renal disease (ESRD), cardiovascular death, nonfatal myocardial infarction (MI), and hospitalization for HF in adults with chronic kidney disease (CKD) associated with type 2 diabetes (T2D). Finerenone is undergoing regulatory assessment in the EU and in China. A phase III trial is investigating finerenone in patients who have HF with preserved ejection fraction.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Mineralocorticoid receptor 53	Antagonist 2,778		16.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Chronic kidney disease associated with type 2 diabetes	Primary		Approved 8,429	Kerendia

C_max

Value	Dose	Co-administered	Analyte	Population
80 μg/L	10 mg 1 times / day steady-state, oral		FINERENONE plasma	Homo sapiens
160 μg/L	20 mg 1 times / day steady-state, oral		FINERENONE plasma	Homo sapiens
5.431 μg/L	1 mg single, oral		FINERENONE plasma	Homo sapiens
12.54 μg/L	2.5 mg single, oral		FINERENONE plasma	Homo sapiens
25.45 μg/L	5 mg single, oral		FINERENONE plasma	Homo sapiens
42.49 μg/L	10 mg single, oral		FINERENONE plasma	Homo sapiens
63.58 μg/L	20 mg single, oral		FINERENONE plasma	Homo sapiens
154.4 μg/L	40 mg single, oral		FINERENONE plasma	Homo sapiens
90.54 μg/L	10 mg 2 times / day multiple, oral		FINERENONE plasma	Homo sapiens
177.3 μg/L	20 mg 2 times / day multiple, oral		FINERENONE plasma	Homo sapiens
287.2 μg/L	40 mg 1 times / day multiple, oral		FINERENONE plasma	Homo sapiens
94.54 μg/L	10 mg 2 times / day multiple, oral		FINERENONE plasma	Homo sapiens
170.6 μg/L	20 mg 2 times / day multiple, oral		FINERENONE plasma	Homo sapiens
258.6 μg/L	40 mg 1 times / day multiple, oral		FINERENONE plasma	Homo sapiens
167.2 μg/L	20 mg 2 times / day multiple, oral	MIDAZOLAM	FINERENONE plasma	Homo sapiens
95.5 μg/L	10 mg single, oral	MIDAZOLAM	FINERENONE plasma	Homo sapiens
105 μg/L	10 mg single, oral	MIDAZOLAM	FINERENONE plasma	Homo sapiens
110 μg/L	10 mg single, oral	MIDAZOLAM	FINERENONE plasma	Homo sapiens
88.4 μg/L	10 mg single, oral	MIDAZOLAM	FINERENONE plasma	Homo sapiens
45.9 μg/L	5 mg single, oral	MIDAZOLAM	FINERENONE plasma	Homo sapiens
47.2 μg/L	5 mg single, oral	MIDAZOLAM	FINERENONE plasma	Homo sapiens
47.6 μg/L	5 mg single, oral	MIDAZOLAM	FINERENONE plasma	Homo sapiens

AUC

Value	Dose	Co-administered	Analyte	Population
343 ng × h/L	10 mg 1 times / day steady-state, oral		FINERENONE plasma	Homo sapiens
686 μg × h/L	20 mg 1 times / day steady-state, oral		FINERENONE plasma	Homo sapiens
12.99 μg × h/L	1 mg single, oral		FINERENONE plasma	Homo sapiens
25.23 μg × h/L	2.5 mg single, oral		FINERENONE plasma	Homo sapiens
51.13 μg × h/L	5 mg single, oral		FINERENONE plasma	Homo sapiens
132.1 μg × h/L	10 mg single, oral		FINERENONE plasma	Homo sapiens
161.4 μg × h/L	20 mg single, oral		FINERENONE plasma	Homo sapiens
470.3 μg × h/L	40 mg single, oral		FINERENONE plasma	Homo sapiens
208.3 μg × h/L	10 mg 2 times / day multiple, oral		FINERENONE plasma	Homo sapiens
318.5 μg × h/L	20 mg 2 times / day multiple, oral		FINERENONE plasma	Homo sapiens
928.7 μg × h/L	40 mg 1 times / day multiple, oral		FINERENONE plasma	Homo sapiens
232.5 μg × h/L	10 mg 2 times / day multiple, oral		FINERENONE plasma	Homo sapiens
420.7 μg × h/L	20 mg 2 times / day multiple, oral		FINERENONE plasma	Homo sapiens
1022 μg × h/L	40 mg 1 times / day multiple, oral		FINERENONE plasma	Homo sapiens
661 μg × h/L	20 mg 2 times / day multiple, oral	MIDAZOLAM	FINERENONE plasma	Homo sapiens
218 μg × h/L	10 mg single, oral	MIDAZOLAM	FINERENONE plasma	Homo sapiens
221 μg × h/L	10 mg single, oral	MIDAZOLAM	FINERENONE plasma	Homo sapiens
352 μg × h/L	10 mg single, oral	MIDAZOLAM	FINERENONE plasma	Homo sapiens
317 μg × h/L	10 mg single, oral	MIDAZOLAM	FINERENONE plasma	Homo sapiens
118 μg × h/L	5 mg single, oral	MIDAZOLAM	FINERENONE plasma	Homo sapiens
150 μg × h/L	5 mg single, oral	MIDAZOLAM	FINERENONE plasma	Homo sapiens
108 μg × h/L	5 mg single, oral	MIDAZOLAM	FINERENONE plasma	Homo sapiens

T_1/2

Value	Dose	Co-administered	Analyte	Population
2.6 h	10 mg 1 times / day steady-state, oral		FINERENONE plasma	Homo sapiens
2.6 h	20 mg 1 times / day steady-state, oral		FINERENONE plasma	Homo sapiens
1.702 h	1 mg single, oral		FINERENONE plasma	Homo sapiens
1.741 h	2.5 mg single, oral		FINERENONE plasma	Homo sapiens
1.874 h	5 mg single, oral		FINERENONE plasma	Homo sapiens
2.066 h	10 mg single, oral		FINERENONE plasma	Homo sapiens
1.776 h	20 mg single, oral		FINERENONE plasma	Homo sapiens
2.834 h	40 mg single, oral		FINERENONE plasma	Homo sapiens
1.779 h	10 mg 2 times / day multiple, oral		FINERENONE plasma	Homo sapiens
1.685 h	20 mg 2 times / day multiple, oral		FINERENONE plasma	Homo sapiens
3.044 h	40 mg 1 times / day multiple, oral		FINERENONE plasma	Homo sapiens
2.564 h	10 mg 2 times / day multiple, oral		FINERENONE plasma	Homo sapiens
2.832 h	20 mg 2 times / day multiple, oral		FINERENONE plasma	Homo sapiens
3.112 h	40 mg 1 times / day multiple, oral		FINERENONE plasma	Homo sapiens
4.295 h	20 mg 2 times / day multiple, oral	MIDAZOLAM	FINERENONE plasma	Homo sapiens
2.21 h	10 mg single, oral	MIDAZOLAM	FINERENONE plasma	Homo sapiens
2.26 h	10 mg single, oral	MIDAZOLAM	FINERENONE plasma	Homo sapiens
2.8 h	10 mg single, oral	MIDAZOLAM	FINERENONE plasma	Homo sapiens
2.78 h	10 mg single, oral	MIDAZOLAM	FINERENONE plasma	Homo sapiens
2.71 h	5 mg single, oral	MIDAZOLAM	FINERENONE plasma	Homo sapiens
3.18 h	5 mg single, oral	MIDAZOLAM	FINERENONE plasma	Homo sapiens
2.29 h	5 mg single, oral	MIDAZOLAM	FINERENONE plasma	Homo sapiens

F_unbound

Value	Dose	Co-administered	Analyte	Population
8.3%			FINERENONE plasma	Homo sapiens

Doses

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Dose	Population	Adverse events
40 mg 1 times / day multiple, oral Highest studied dose	healthy, ADULT
40 mg single, oral Highest studied dose	healthy, ADULT
20 mg 1 times / day multiple, oral Studied dose	unhealthy, ADULT	Disc. AE: Adverse event, Adverse event... Other AEs: Adverse event...

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AEs

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AE	Significance	Dose	Population
Adverse event	2.2% Disc. AE	20 mg 1 times / day multiple, oral Studied dose	unhealthy, ADULT
Hyperkalemia	2.3% Disc. AE	20 mg 1 times / day multiple, oral Studied dose	unhealthy, ADULT
Adverse event	26% Disc. AE	20 mg 1 times / day multiple, oral Studied dose	unhealthy, ADULT
Adverse event	27.2%	20 mg 1 times / day multiple, oral Studied dose	unhealthy, ADULT
Adverse event (other than Hyperkalemia)	4.7% Disc. AE	20 mg 1 times / day multiple, oral Studied dose	unhealthy, ADULT

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Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1,737 inducer 781 inhibitor 1,587	inhibitor 1,767	inhibitor 1,852	inhibitor 1,612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A1 110 UGT2B7 146 CYP2C19 1,478 P-gp 1,461 BCRP 699 CYP1A2 1,524 OCT2 647 OATP1B1 788 OAT1 599 OATP1B3 706 OCT1 512 MATE2K UGT1A1 204 CYP2B6 810 MATE1 306 CYP2C8 911 OAT3 642 UGT1A6 108 UGT2B4 19 UGT1A4 77 UGT1A9 116	P-gp 1,537 OATP1B1 406 OCT1 327 BCRP 561 OATP1B3 350 CYP1A1 349 CYP3A5 395 CYP3A7 110 CYP2C8 693	CYP1A2 701 CYP2B6 547 CYP2C19 293

Drug as perpetrator

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Target	Modality	Activity
CYP1A2 1,692	inhibitor 3,277	no [IC50 >50 uM]
CYP2B6 1,001	inhibitor 3,277	no [IC50 >50 uM]
CYP2D6 1,891	inhibitor 3,277	no [IC50 >50 uM]
UGT1A1 254	inhibitor 3,277	no [IC50 >50 uM]
UGT1A4 80	inhibitor 3,277	no [IC50 >50 uM]

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Drug as victim

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Target	Modality	Activity	Clinical evidence
CYP3A4 1,737	substrate 3,367	major	yes (co-administration study)
CYP2C8 693	substrate 3,367	minor	yes (co-administration study)
BCRP 561	substrate 3,367	no
OATP1B1 406	substrate 3,367	no
OATP1B3 350	substrate 3,367	no

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Tox targets

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Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1,647	inhibitor 1,626

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PubMed

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Title	Date	PubMed
Discovery of BAY 94-8862: a nonsteroidal antagonist of the mineralocorticoid receptor for the treatment of cardiorenal diseases.	2012 Aug	22791416
Renin-angiotensin system blockade: Finerenone.	2017 Apr	28577743

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Patents

Sample Use Guides

In Vivo Use Guide

The recommended starting dosage is 10 mg or 20 mg orally once daily based on estimated glomerular filtration rate (eGFR) and serum potassium thresholds. (2.1) • Increase dosage after 4 weeks to the target dose of 20 mg once daily, based on eGFR and serum potassium thresholds. (2.3) • Tablets may be taken with or without food

Route of Administration: Oral

In Vitro Use Guide

Finerenone had an IC50 of 17 nM in the MR, but no activity up to 10 uM in the other steroid hormone receptors.

Substance Class	Chemical
Record UNII	DE2O63YV8R
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

FINERENONE

Official Name

English

finerenone [INN]

Common Name

English

1,6-NAPHTHYRIDINE-3-CARBOXAMIDE, 4-(4-CYANO-2-METHOXYPHENYL)-5-ETHOXY-1,4-DIHYDRO-2,8-DIMETHYL-, (4S)-

Systematic Name

English

BAY 94-8862

Code

English

FINERENONE [ORANGE BOOK]

Common Name

English

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Code System

Code

Type

Description

EPA CompTox

DTXSID10146928

PRIMARY

USAN

BC-45

PRIMARY

NCI_THESAURUS

C169981

PRIMARY

CAS

1050477-31-0

PRIMARY

WIKIPEDIA

Finerenone

PRIMARY

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Related Record

Type

Details


					DE2O63YV8R

FINERENONE

EXCRETED UNCHANGED

Qualification:

URINE

Amount:

0.825 % (average)
of total radioactivity AUCs


					33M0S99YTT

MINERALOCORTICOID RECEPTOR

TARGET -> INHIBITOR

Amount:


					L0423Z5LDW

CYTOCHROME P450 2C8

METABOLIC ENZYME -> SUBSTRATE

Amount:


					PUO0521HZV

CYTOCHROME P450 3A4

METABOLIC ENZYME -> SUBSTRATE

Interaction Type:

MAJOR

Amount:


					DE2O63YV8R

FINERENONE

EXCRETED UNCHANGED

Qualification:

FECAL

Amount:

0.184 % (average)
of total radioactivity AUCs

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Related Record

Type

Details


					CW6UE4TAF8

(4S)-4-(4-CYANO-2-METHOXY-PHENYL)-5-ETHOXY-2,3-DIHYDROXY-8-(HYDROXYMETHYL)-2-METHYL-1,4-DIHYDRO-1,6-NAPHTHYRIDINE-3-CARBOXAMIDE

METABOLITE -> PARENT

Qualification:

URINE

Amount:

2.72 % (average)
of dose


					YR4K8UH3WV

1,6-NAPHTHYRIDINE-8-CARBOXYLIC ACID, 3-(AMINOCARBONYL)-4-(4-CYANO-2-METHOXYPHENYL)-5-ETHOXY-2-METHYL-, (4S)-

METABOLITE -> PARENT

Qualification:

PLASMA

Amount:

8.98 % (average)
of total radioactivity AUC


					MUC5R84538

1,6-NAPHTHYRIDINE-3-CARBOXAMIDE, 4-(4-CYANO-2-METHOXYPHENYL)-5-ETHOXY-8-(HYDROXYMETHYL)-2-METHYL-, (4S)-

METABOLITE -> PARENT

Qualification:

URINE

Amount:

13.1 % (average)
of dose


					CW6UE4TAF8

(4S)-4-(4-CYANO-2-METHOXY-PHENYL)-5-ETHOXY-2,3-DIHYDROXY-8-(HYDROXYMETHYL)-2-METHYL-1,4-DIHYDRO-1,6-NAPHTHYRIDINE-3-CARBOXAMIDE

METABOLITE -> PARENT

Qualification:

PLASMA

Amount:

1.4 % (average)
of total radioactivity AUC


					F7FF82TDC8

(4S)-4-(4-CYANO-2-METHOXY-PHENYL)-5-ETHOXY-2,3-DIHYDROXY-2,8-DIMETHYL-1,4-DIHYDRO-1,6-NAPHTHYRIDINE-3-CARBOXAMIDE

METABOLITE -> PARENT

Qualification:

PLASMA

Amount:

2.4 % (average)
of total radioactivity AUC

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Related Record

Type

Details


					DE2O63YV8R

FINERENONE

ACTIVE MOIETY

Amount:

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SMILES

InChI

CNS Activity

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Funbound

Doses

AEs

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

Tox targets

PubMed

Patents

Sample Use Guides

C_max

T_1/2

F_unbound

Drug as perpetrator