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 817		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 8307	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 1.32148796E12

C_max

Value	Dose	Co-administered	Analyte	Population
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
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

AUC

Value	Dose	Co-administered	Analyte	Population
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
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

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	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
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

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	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
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

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 n = 9 Health Status: healthy Age Group: 24 to 54 years Sex: M Population Size: 9 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 n = 65 Health Status: unhealthy Condition: transthyretin familial amyloid polyneuropathy Age Group: mean 39.8 years Sex: M+F Population Size: 65 Sources: https://pubmed.ncbi.nlm.nih.gov/22843282/	Disc. AE: Urinary tract infection... Other AEs: Neuralgia, Diarrhea... AEs leading to discontinuation/dose reduction: Urinary tract infection (3.1%) Other AEs: Neuralgia (3.1%) 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%) 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 n = 21 Health Status: unhealthy Condition: non-Val30Met transthyretin amyloidosis Age Group: mean 63.1 years Sex: M+F Population Size: 21 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 n = 176 Health Status: unhealthy Condition: transthyretin mediated amyloidosis Age Group: median age 75 years Sex: M+F Population Size: 176 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 n = 176 Health Status: unhealthy Condition: transthyretin mediated amyloidosis Age Group: median age 75 years Sex: M+F Population Size: 176 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 n = 88 Health Status: unhealthy Condition: transthyretin mediated amyloidosis Age Group: median age 75 years Sex: M+F Population Size: 88 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 n = 127 Health Status: unhealthy Condition: transthyretin mediated amyloidosis Age Group: median age 75 years Sex: M+F Population Size: 127 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 (mean) 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 n = 264 Health Status: unhealthy Condition: transthyretin mediated amyloidosis Age Group: median age 75 years Sex: M+F Population Size: 264 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 753	inhibitor 1695	inhibitor 1789	inhibitor 1570

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
BCRP 678 OAT1 584 OAT3 625 P-gp 1401 OCT2 630 OATP1B1 770 OATP1B3 691 MATE1 302 MATE2 259 CYP1A2 1463 CYP2C19 1410 CYP2C8 869 CYP2B6 770 CYP3A4/5 261 UGT1A1 200 UGT1A4 76 UGT1A6 107 UGT1A9 115 UGT2B7 145	P-gp 1491 BCRP 545 OAT1 314 OAT3 328 OCT2 336 OATP1B1 389 OATP1B3 333 MATE1 131 MATE2 93 UGT1A9 378 UGT1A1 417 UGT1A3 421 UGT1A6 306 UGT1A7 235 UGT1A8 282 UGT2B7 387	CYP1A2 671 CYP2B6 521

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP2C8 923	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000PharmR.pdf#page=28 Page: 28.0	moderate [Ki 19 uM]
UGT2B7 156	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=18 Page: 18.0	no [IC50 83 uM]
UGT1A4 79	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=18 Page: 18.0	no [IC50 86 uM]
UGT1A6 139	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=18 Page: 18.0	no [IC50 >100 uM]
UGT1A9 120	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=18 Page: 18.0	no [IC50 >100 uM]
CYP1A2 1620	inducer 1515 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=18 Page: 18.0	no
CYP2B6 946	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=18 Page: 18.0	no
MATE1 304	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=18 Page: 18.0	no
MATE2 259	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=18 Page: 18.0	no
OATP1B1 785	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=18 Page: 18.0	no
OATP1B3 700	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=18 Page: 18.0	no
OCT2 631	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=18 Page: 18.0	no
P-gp 1588	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=18 Page: 18.0	no
CYP1A2 1620	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000PharmR.pdf#page=28 Page: 28.0	weak [Ki >100 uM]
CYP2C19 1484	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000PharmR.pdf#page=28 Page: 28.0	weak [Ki >100 uM]
CYP2C9 1747	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000PharmR.pdf#page=28 Page: 28.0	weak [Ki >100 uM]
CYP2D6 1826	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000PharmR.pdf#page=28 Page: 28.0	weak [Ki >100 uM]
CYP3A4/5 314	inhibitor 3185 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 946	inducer 1515 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 1857	inducer 1515 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 751	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=17 Page: 17.0	yes [IC50 1.16 uM]
OAT3 627	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=18 Page: 18.0	yes [IC50 2.36 uM]
UGT1A1 249	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=8 Page: 8,18	yes [IC50 30 uM]
OAT1 588	inhibitor 3185 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 417	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=11 Page: 11.0	major
UGT1A3 421	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=11 Page: 11.0	major
UGT1A9 378	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=11 Page: 11.0	major
UGT1A6 306	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=11 Page: 11.0	minor
UGT1A7 235	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=11 Page: 11.0	minor
UGT1A8 282	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=11 Page: 11.0	minor
UGT2B7 387	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=11 Page: 11.0	minor
BCRP 545	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=11 Page: 11.0	no
MATE1 131	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=11 Page: 11.0	no
MATE2 93	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=11 Page: 11.0	no
OAT1 314	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=11 Page: 11.0	no
OAT3 328	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=11 Page: 11.0	no
OATP1B1 389	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=11 Page: 11.0	no
OATP1B3 333	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=11 Page: 11.0	no
OCT2 336	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=11 Page: 11.0	no
P-gp 1491	substrate 3264 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 1603	inhibitor 1584 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
Familial amyloid polyneuropathy: new developments in genetics and treatment.	1996 Oct	8894411
Evidence for direct binding of fatty acids and eicosanoids to human peroxisome proliferators-activated receptor alpha.	1999 Jul 14	10403814
Tafamidis, a potent and selective transthyretin kinetic stabilizer that inhibits the amyloid cascade.	2012 Jun 12	22645360

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 `Sun Dec 18 19:46:41 UTC 2022` Edited by `admin` on `Sun Dec 18 19:46:41 UTC 2022`
Record UNII	8FG9H9D31J
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

TAFAMIDIS

Official 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

FX-006

Code

English

tafamidis [INN]

Common Name

English

TAFAMIDIS [USAN]

Common Name

English

Classification Tree Code System Code

WHO-ATC

N07XX08