TAFAMIDIS MEGLUMINE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C14H7Cl2NO3.C7H17NO5
Molecular Weight	503.33
Optical Activity	UNSPECIFIED
Defined Stereocenters	4 / 4
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.OC(=O)C1=CC=C2N=C(OC2=C1)C3=CC(Cl)=CC(Cl)=C3

InChI

InChIKey=DQJDBUPLRMRBAB-WZTVWXICSA-N

InChI=1S/C14H7Cl2NO3.C7H17NO5/c15-9-3-8(4-10(16)6-9)13-17-11-2-1-7(14(18)19)5-12(11)20-13;1-8-2-4(10)6(12)7(13)5(11)3-9/h1-6H,(H,18,19);4-13H,2-3H2,1H3/t;4-,5+,6+,7+/m.0/s1

HIDE SMILES / InChI

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 828		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 8429	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
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 781	inhibitor 1767	inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
BCRP 699 OAT1 599 OAT3 642 P-gp 1461 OCT2 647 OATP1B1 788 OATP1B3 706 MATE1 306 MATE2 263 CYP1A2 1524 CYP2C19 1478 CYP2C8 911 CYP2B6 810 CYP3A4/5 278 UGT1A1 204 UGT1A4 77 UGT1A6 108 UGT1A9 116 UGT2B7 146	P-gp 1537 BCRP 561 OAT1 326 OAT3 339 OCT2 355 OATP1B1 406 OATP1B3 350 MATE1 135 MATE2 96 UGT1A9 380 UGT1A1 418 UGT1A3 422 UGT1A6 307 UGT1A7 236 UGT1A8 283 UGT2B7 389	CYP1A2 701 CYP2B6 547

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000PharmR.pdf#page=28 Page: 28.0	moderate [Ki 19 uM]
UGT2B7 157	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=18 Page: 18.0	no [IC50 83 uM]
UGT1A4 80	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=18 Page: 18.0	no [IC50 86 uM]
UGT1A6 141	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=18 Page: 18.0	no [IC50 >100 uM]
UGT1A9 121	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=18 Page: 18.0	no [IC50 >100 uM]
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=18 Page: 18.0	no
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=18 Page: 18.0	no
MATE1 308	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=18 Page: 18.0	no
MATE2 263	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=18 Page: 18.0	no
OATP1B1 803	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=18 Page: 18.0	no
OATP1B3 715	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=18 Page: 18.0	no
OCT2 648	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=18 Page: 18.0	no
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=18 Page: 18.0	no
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000PharmR.pdf#page=28 Page: 28.0	weak [Ki >100 uM]
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000PharmR.pdf#page=28 Page: 28.0	weak [Ki >100 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000PharmR.pdf#page=28 Page: 28.0	weak [Ki >100 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000PharmR.pdf#page=28 Page: 28.0	weak [Ki >100 uM]
CYP3A4/5 335	inhibitor 3277 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 1001	inducer 1573 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 1925	inducer 1573 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 773	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=17 Page: 17.0	yes [IC50 1.16 uM]
OAT3 644	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=18 Page: 18.0	yes [IC50 2.36 uM]
UGT1A1 254	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=8 Page: 8,18	yes [IC50 30 uM]
OAT1 603	inhibitor 3277 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 418	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=11 Page: 11.0	major
UGT1A3 422	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=11 Page: 11.0	major
UGT1A9 380	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=11 Page: 11.0	major
UGT1A6 307	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=11 Page: 11.0	minor
UGT1A7 236	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=11 Page: 11.0	minor
UGT1A8 283	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=11 Page: 11.0	minor
UGT2B7 389	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=11 Page: 11.0	minor
BCRP 561	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=11 Page: 11.0	no
MATE1 135	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=11 Page: 11.0	no
MATE2 96	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=11 Page: 11.0	no
OAT1 326	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=11 Page: 11.0	no
OAT3 339	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=11 Page: 11.0	no
OATP1B1 406	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=11 Page: 11.0	no
OATP1B3 350	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=11 Page: 11.0	no
OCT2 355	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000ClinPharmR.pdf#page=11 Page: 11.0	no
P-gp 1537	substrate 3367 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 1647	inhibitor 1626 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
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
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).

Name

Type

Language

TAFAMIDIS MEGLUMINE

Official Name

English

TAFAMIDIS MEGLUMINE [MI]

Common Name

English

TAFAMIDIS MEGLUMINE [ORANGE BOOK]

Common Name

English

D-GLUCO-2,3,4,5,6-PENTAHYDROXY-N-METHYLHEXAN-1-AMINIUM 2-(3,5-DICHLOROPHENYL)BENZOXAZOLE-6-CARBOXYLATE

Common Name

English

VYNDAQEL

Brand Name

English

TAFAMIDIS MEGLUMINE [USAN]

Common Name

English

Tafamidis meglumine [WHO-DD]

Common Name

English

TAFAMIDIS MEGLUMINE [JAN]

Common Name

English

FX-1006A

Code

English

D-GLUCITOL, 1-DEOXY-1-(METHYLAMINO)-, 2-(3,5-DICHLOROPHENYL)-6-BENZOXAZOLECARBOXYLATE (1:1)

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

363312