TAFAMIDIS

Details

Stereochemistry	ACHIRAL
Molecular Formula	C14H7Cl2NO3
Molecular Weight	308.116
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC(=O)C1=CC=C2N=C(OC2=C1)C3=CC(Cl)=CC(Cl)=C3

InChI

InChIKey=TXEIIPDJKFWEEC-UHFFFAOYSA-N

InChI=1S/C14H7Cl2NO3/c15-9-3-8(4-10(16)6-9)13-17-11-2-1-7(14(18)19)5-12(11)20-13/h1-6H,(H,18,19)

HIDE SMILES / InChI

Molecular Formula	C14H7Cl2NO3
Molecular Weight	308.116
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002294/WC500117862.pdf | https://www.ncbi.nlm.nih.gov/pubmed/22645721 | https://www.ncbi.nlm.nih.gov/pubmed/22645360

Tafamidis meglumine (Vyndaqel®, Pfizer) is a novel, first-in-class drug for the treatment of transthyretin familial amyloid polyneuropathy (TTR-FAP), a rare neurodegenerative disorder characterized by progressive sensory, motor and autonomic impairment that is ultimately fatal. Pathogenic mutations in the transthyretin (TTR) protein lead to destabilization of its tetrameric structure and subsequent formation of amyloid aggregates. Tafamidis is a small-molecule inhibitor that binds selectively to TTR in human plasma and kinetically stabilizes the tetrameric structure of both wild-type TTR and a number of different mutants. Clinical trials indicate that tafamidis slows disease progression in patients with TTR-FAP and reduces the burden of disease, demonstrating improvement in small and large nerve fiber function, modified body mass index and lower extremity neurological examination. Tafamidis meglumine has been launched for TTR FAP in the EU, Japan, Argentina, Malta and Mexico, and is preregistration in the US for this indication.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Transthyretin 6 Target ID: CHEMBL3194 Sources: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/002294/WC500117838.pdf	Modulator 846		2.0 nM [Kd]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Familial amyloid polyneuropathy 2 Sources: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/002294/WC500117838.pdf https://www.ncbi.nlm.nih.gov/pubmed/26894299 https://www.ncbi.nlm.nih.gov/pubmed/22645721	Primary		Approved 8583	Vyndaqel Approved Use Vyndaqel is indicated for the treatment of transthyretin amyloidosis in adult patients with stage 1 symptomatic polyneuropathy to delay peripheral neurologic impairment. Launch Date 2011

C_max

Value	Dose	Co-administered	Analyte	Population
3 μg/mL DRUG LABEL https://www.pfizer.ca/sites/default/files/202002/Vyndaqel_PM_228368_20Jan2020_EN.pdf	20 mg 1 times / day steady-state, oral dose: 20 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		TAFAMIDIS MEGLUMINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
11.99 μg/mL DRUG LABEL https://www.pfizer.ca/sites/default/files/202002/Vyndaqel_PM_228368_20Jan2020_EN.pdf	80 mg 1 times / day steady-state, oral dose: 80 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		TAFAMIDIS MEGLUMINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
60.39 μg × h/mL DRUG LABEL https://www.pfizer.ca/sites/default/files/202002/Vyndaqel_PM_228368_20Jan2020_EN.pdf	20 mg 1 times / day steady-state, oral dose: 20 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		TAFAMIDIS MEGLUMINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
241.5 μg × h/mL DRUG LABEL https://www.pfizer.ca/sites/default/files/202002/Vyndaqel_PM_228368_20Jan2020_EN.pdf	80 mg 1 times / day steady-state, oral dose: 80 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		TAFAMIDIS MEGLUMINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
57 h DRUG LABEL https://www.pfizer.ca/sites/default/files/202002/Vyndaqel_PM_228368_20Jan2020_EN.pdf	20 mg 1 times / day steady-state, oral dose: 20 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		TAFAMIDIS MEGLUMINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
57 h DRUG LABEL https://www.pfizer.ca/sites/default/files/202002/Vyndaqel_PM_228368_20Jan2020_EN.pdf	80 mg 1 times / day steady-state, oral dose: 80 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		TAFAMIDIS MEGLUMINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
1% DRUG LABEL https://www.pfizer.ca/sites/default/files/202002/Vyndaqel_PM_228368_20Jan2020_EN.pdf	20 mg 1 times / day steady-state, oral dose: 20 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		TAFAMIDIS MEGLUMINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
1% DRUG LABEL https://www.pfizer.ca/sites/default/files/202002/Vyndaqel_PM_228368_20Jan2020_EN.pdf	80 mg 1 times / day steady-state, oral dose: 80 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		TAFAMIDIS MEGLUMINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
480 mg 1 times / day single, oral Highest studied dose Dose: 480 mg, 1 times / day Route: oral Route: single Dose: 480 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000MedR.pdf	healthy, 24 to 54 years Health Status: healthy Age Group: 24 to 54 years Sex: M Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000MedR.pdf	Other AEs: Hordeolum... Other AEs: Hordeolum (grade 1) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000MedR.pdf
20 mg 1 times / day multiple, oral Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22843282/	unhealthy, mean 39.8 years Health Status: unhealthy Age Group: mean 39.8 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/22843282/	Disc. AE: Urinary tract infection... Other AEs: Diarrhea, Urinary tract infection... AEs leading to discontinuation/dose reduction: Urinary tract infection (3.1%) Other AEs: Diarrhea (26.2%) Urinary tract infection (23.1%) Pain in extremity (16.9%) Influenza (15.4%) Headache (15.4%) Nasopharyngitis (13.8%) Upper abdominal pain (12.3%) Nausea (12.3%) Vomiting (10.8%) Lacrimation decreased (9.2%) Myalgia (7.7%) Punctate keratitis (7.7%) Back pain (7.7%) Vaginal infection (6.2%) Peripheral edema (6.2%) Constipation (6.2%) Pharyngitis (6.2%) Upper respiratory tract infection (6.2%) Thermal burn (6.2%) Anxiety (6.2%) Depression (6.2%) Erectile dysfunction (6.2%) Paresthesia (4.6%) Abdominal pain (4.6%) Weight decreased (4.6%) Vertigo (4.6%) Neuralgia (3.1%) Pharyngolaryngeal pain (3.1%) Muscle spasms (3.1%) AV block first degree (3.1%) Dizziness (3.1%) Hypoesthesia (1.5%) Sources: https://pubmed.ncbi.nlm.nih.gov/22843282/
20 mg 1 times / day multiple, oral Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/24101373/	unhealthy, mean 63.1 years Health Status: unhealthy Age Group: mean 63.1 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/24101373/	Disc. AE: Transient ischemic attack... Other AEs: Fall, Diarrhea... AEs leading to discontinuation/dose reduction: Transient ischemic attack (grade 1, 4.8%) Other AEs: Fall (24%) Diarrhea (24%) Pain in extremity (19%) Dizziness (14%) Dyspnea (14%) Vomiting (14%) Constipation (14%) Ankle fracture (4.8%) Malaise (4.8%) Urinary retention (4.8%) Sources: https://pubmed.ncbi.nlm.nih.gov/24101373/
80 mg 1 times / day multiple, oral Recommended Dose: 80 mg, 1 times / day Route: oral Route: multiple Dose: 80 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000MedR.pdf	unhealthy, median age 75 years Health Status: unhealthy Age Group: median age 75 years Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000MedR.pdf	Other AEs: Diarrhea, Upper abdominal pain... Other AEs: Diarrhea (14.2%) Upper abdominal pain (8%) Urinary tract infection (12.5%) Hypersensitivity (14.8%) Hepatotoxicity (21.6%) Dysfunction thyroid (9.1%) Cardiac arrhythmia (37.5%) Hypotension orthostatic (42%) Infection (65.9%) Pancreatitis (0.6%) Pneumonia (15.3%) Coordination and balance disturbances (9.1%) Balance disorder (8.5%) Fall (24.4%) Accidental injury (35.2%) Falling (30%) Lens disorder (10.2%) Hepatotoxicity (21.6%) Dysfunction thyroid (9.1%) Asthenic conditions (25.6%) Retinol binding protein increased (44%) AST increased (7.39%) ALP increased (6.25%) Bilirubin total increased (0.57%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000MedR.pdf
80 mg 1 times / day multiple, oral Recommended Dose: 80 mg, 1 times / day Route: oral Route: multiple Dose: 80 mg, 1 times / day Sources: https://www.ema.europa.eu/en/documents/product-information/vyndaqel-epar-product-information_en.pdf	unhealthy, median age 75 years Health Status: unhealthy Age Group: median age 75 years Sex: M+F Sources: https://www.ema.europa.eu/en/documents/product-information/vyndaqel-epar-product-information_en.pdf	Other AEs: Flatulence, Liver function test increased... Other AEs: Flatulence (4.5%) Liver function test increased (3.4%) Sources: https://www.ema.europa.eu/en/documents/product-information/vyndaqel-epar-product-information_en.pdf
20 mg 1 times / day multiple, oral Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000MedR.pdf	unhealthy, median age 75 years Health Status: unhealthy Age Group: median age 75 years Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000MedR.pdf	Other AEs: Diarrhea, Upper abdominal pain... Other AEs: Diarrhea (11.4%) Upper abdominal pain (9.1%) Urinary tract infection (11.4%) Hypersensitivity (10.2%) Hepatotoxicity (26.1%) Dysfunction thyroid (6.8%) Cardiac arrhythmia (33%) Hypotension orthostatic (48.9%) Infection (55.7%) Pneumonia (12.5%) Coordination and balance disturbances (2.3%) Balance disorder (2.3%) Fall (30.7%) Accidental injury (42%) Falling (33%) Lens disorder (8%) Hepatotoxicity (26.1%) Dysfunction thyroid (6.8%) Asthenic conditions (23.9%) Retinol binding protein increased (51%) AST increased (3.41%) ALP increased (5.68%) Bilirubin total increased (1.14%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000MedR.pdf
20 mg 1 times / day multiple, oral Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: https://www.ema.europa.eu/en/documents/product-information/vyndaqel-epar-product-information_en.pdf	unhealthy, median age 75 years Health Status: unhealthy Age Group: median age 75 years Sex: M+F Sources: https://www.ema.europa.eu/en/documents/product-information/vyndaqel-epar-product-information_en.pdf	Other AEs: Urinary tract infection, Vaginal infection... Other AEs: Urinary tract infection (grade 1-2, >10) Vaginal infection (grade 1-2, >10) Diarrhoea (grade 1-2, >10) Upper abdominal pain (grade 1-2, >10) Sources: https://www.ema.europa.eu/en/documents/product-information/vyndaqel-epar-product-information_en.pdf
50 mg 1 times / day multiple, oral Dose: 50 mg, 1 times / day Route: oral Route: multiple Dose: 50 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000MedR.pdf	unhealthy, median age 75 years Health Status: unhealthy Age Group: median age 75 years Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000MedR.pdf	Other AEs: Infection, Pneumonia... Other AEs: Infection (62.5%) Pneumonia (14.4%) Falling (31.1%) Lens disorder (9.5%) Hepatotoxicity (23.1%) Dysfunction thyroid (8.3%) Asthenic conditions (25%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000MedR.pdf

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 1087	inhibitor 2438	inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
BCRP 910 OAT1 725 OAT3 747 P-gp 1741 OCT2 779 OATP1B1 1079 OATP1B3 961 MATE1 415 MATE2 267 CYP1A2 2153 CYP2C19 2057 CYP2C8 1057 CYP2B6 926 CYP3A4/5 296 UGT1A1 246 UGT1A4 98 UGT1A6 136 UGT1A9 148 UGT2B7 197	P-gp 2052 BCRP 697 OAT1 395 OAT3 391 OCT2 434 OATP1B1 503 OATP1B3 435 MATE1 182 MATE2 98 UGT1A9 423 UGT1A1 479 UGT1A3 470 UGT1A6 343 UGT1A7 249 UGT1A8 323 UGT2B7 456	CYP1A2 832 CYP2B6 669

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP2C8 1117	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000PharmR.pdf#page=28 Page: 28.0	moderate [Ki 19 uM]
UGT2B7 210	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=18 Page: 18.0	no [IC50 83 uM]
UGT1A4 100	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=18 Page: 18.0	no [IC50 86 uM]
UGT1A6 171	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=18 Page: 18.0	no [IC50 >100 uM]
UGT1A9 155	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=18 Page: 18.0	no [IC50 >100 uM]
CYP1A2 2333	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=18 Page: 18.0	no
CYP2B6 1160	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=18 Page: 18.0	no
MATE1 416	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=18 Page: 18.0	no
MATE2 267	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=18 Page: 18.0	no
OATP1B1 1095	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=18 Page: 18.0	no
OATP1B3 970	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=18 Page: 18.0	no
OCT2 782	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=18 Page: 18.0	no
P-gp 1932	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=18 Page: 18.0	no
CYP1A2 2333	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000PharmR.pdf#page=28 Page: 28.0	weak [Ki >100 uM]
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000PharmR.pdf#page=28 Page: 28.0	weak [Ki >100 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000PharmR.pdf#page=28 Page: 28.0	weak [Ki >100 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000PharmR.pdf#page=28 Page: 28.0	weak [Ki >100 uM]
CYP3A4/5 357	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000PharmR.pdf#page=28 Page: 28.0	weak [Ki >100 uM]	no (co-administration study) Comment: clinical DDI study with midazolam, a probe CYP3A substrate, did not show any clinically significant impact on the PK of midazolam and its active metabolite when co-administered Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000PharmR.pdf#page=28 Page: 28.0
CYP2B6 1160	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=18 Page: 18.0	yes [EC50 25 uM]	unlikely Comment: maximal decrease in AUC of CYP2B6 substrates using static-mechanistic model was predicted to be 15% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=18 Page: 18.0
CYP3A4 2633	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=18 Page: 18.0	yes [EC50 28 uM]	unlikely (co-administration study) Comment: co-administration wtih midazolam did not show any clinically significant impact on PK of midazolam; maximal decrease in AUC of CYP3A4 substrates using static-mechanistic model was predicted to be 9% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=18 Page: 18.0
BCRP 985	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=17 Page: 17.0	yes [IC50 1.16 uM]
OAT3 749	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=18 Page: 18.0	yes [IC50 2.36 uM]
UGT1A1 303	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=8 Page: 8,18	yes [IC50 30 uM]
OAT1 730	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=8 Page: 8.0	yes

Drug as victim

Target	Modality	Activity
UGT1A1 479	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=11 Page: 11.0	major
UGT1A3 470	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=11 Page: 11.0	major
UGT1A9 423	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=11 Page: 11.0	major
UGT1A6 343	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=11 Page: 11.0	minor
UGT1A7 249	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=11 Page: 11.0	minor
UGT1A8 323	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=11 Page: 11.0	minor
UGT2B7 456	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=11 Page: 11.0	minor
BCRP 697	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=11 Page: 11.0	no
MATE1 182	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=11 Page: 11.0	no
MATE2 98	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=11 Page: 11.0	no
OAT1 395	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=11 Page: 11.0	no
OAT3 391	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=11 Page: 11.0	no
OATP1B1 503	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=11 Page: 11.0	no
OATP1B3 435	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=11 Page: 11.0	no
OCT2 434	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=11 Page: 11.0	no
P-gp 2052	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=11 Page: 11.0	no

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000PharmR.pdf#page=22 Page: 22.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:78538	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:78538
ChemicalBook	CB52484674	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB52484674
MolPort	MolPort-027-352-897	https://www.molport.com/shop/molecule-link/MolPort-027-352-897
ZINC	ZINC000043206271	http://zinc15.docking.org/substances/ZINC000043206271

PubMed

Title	Date	PubMed
A peculiar form of peripheral neuropathy; familiar atypical generalized amyloidosis with special involvement of the peripheral nerves.	1952 Sep	12978172
Fibril in senile systemic amyloidosis is derived from normal transthyretin.	1990 Apr	2320592
Familial amyloid polyneuropathy: new developments in genetics and treatment.	1996 Oct	8894411
Variant-sequence transthyretin (isoleucine 122) in late-onset cardiac amyloidosis in black Americans.	1997 Feb 13	9017939
Evidence for direct binding of fatty acids and eicosanoids to human peroxisome proliferators-activated receptor alpha.	1999 Jul 14	10403814
The pathway by which the tetrameric protein transthyretin dissociates.	2005 Nov 29	16300401
Tafamidis, a potent and selective transthyretin kinetic stabilizer that inhibits the amyloid cascade.	2012 Jun 12	22645360
AG10 inhibits amyloidogenesis and cellular toxicity of the familial amyloid cardiomyopathy-associated V122I transthyretin.	2013 Jun 11	23716704

Patents

Sample Use Guides

In Vivo Use Guide

The recommended dose of tafamidis meglumine is 20 mg orally once daily.

Route of Administration: Oral

In Vitro Use Guide

Tafamidis effectively inhibited fibril formation induced by acid denaturation in a concentration-dependent manner with similar potency for wild-type TTR, V30M TTR and V122I TTR, reaching its EC50 at a tafamidis:TTR stoichiometry of <1 (EC50 was in the range of 2.7-3.2 uM, corresponding to a tafamidis: TTR stoichiometry range of 0.75-0.9).

Substance Class	Chemical Created by `admin` on `Wed Apr 02 08:45:22 GMT 2025` Edited by `admin` on `Wed Apr 02 08:45:22 GMT 2025`
Record UNII	8FG9H9D31J
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

TAFAMIDIS

Official Name

English

FX-006

Preferred Name

English

FX006

Code

English

Tafamidis [WHO-DD]

Common Name

English

VYNDAMAX

Brand Name

English

FX1006

Code

English

FX-1006

Code

English

2-(3,5-Dichlorophenyl)benzoxazole-6-carboxylic acid

Systematic Name

English

6-BENZOXAZOLECARBOXYLIC ACID, 2-(3,5-DICHLOROPHENYL)-

Common Name

English

TAFAMIDIS [MART.]

Common Name

English

TAFAMIDIS [ORANGE BOOK]

Common Name

English

TAFAMIDIS [JAN]

Common Name

English

TAFAMIDIS [MI]

Common Name

English

FX-1005

Code

English

tafamidis [INN]

Common Name

English

TAFAMIDIS [USAN]

Common Name

English

Classification Tree Code System Code

WHO-ATC

N07XX08