Table 2. List of FDA-approved or... | Rockefeller University Press

Table 2.

List of FDA-approved or late-development retinoids with known common side effect profiles at pharmacologic doses

Category	Compound	Type	Receptor specificity	FDA approval	Route	Highest stage	Known adverse events
RAR agonist	Tretinoin	Natural	RARα/β/γ	APL	Oral	FDA approved	L T R B D
RAR agonist	Palovarotene	Synthetic	RARγ	Fibrodysplasia ossificans progressiva	Oral	FDA approved	D B
RAR agonist	Tamibarotene (Am80)	Synthetic	RARα	None	Oral	Phase III	L T R B D
RAR agonist	Fenretinide	Synthetic	RARα/β/γ	None	Oral	Phase III	L D V I
RAR agonist	IRX5183	Synthetic	RARα	None	Oral	Phase II	L I
RAR agonist	Amsilarotene (TAC-101)	Synthetic	RARα	None	Oral	Phase II	L
RAR agonist	Trifarotene	Synthetic	RARγ	Acne vulgaris	Topical	FDA approved	Mild D
RAR agonist	Adapalene	Synthetic	RARβ/γ	Acne vulgaris	Topical	FDA approved	Mild D
RAR agonist	Tazarotene	Synthetic	RARβ/γ	Acne vulgaris/psoriasis	Topical	FDA approved	D T
RAR agonist	Alitretinoin (9-cis RA)	Natural	RXRα/β/γ	Cutaneous Kaposi sarcoma	Topical	FDA approved	D
RXR agonist	Bexarotene	Synthetic	RXRα/β/γ	CTCL	Oral	FDA approved	L T D V H
Non-nuclear pathway	Isotretinoin (Accutane, 13-cis RA)	Natural	None	Acne vulgaris	Oral	FDA approved	D V N B
RA biosynthesis	Disulfiram	Synthetic	ALDH1a1/2 inhibitor	Alcohol aversion	Oral	FDA approved	I
RA biosynthesis	WIN18446	Synthetic	ALDH1a1,2,3	None	Oral	Phase I	Male infertility
RA biosynthesis	Talarazole	Synthetic	Cyp26 inhibitor	None	Oral	Phase II	Acutely toxic
RAR antagonist	AGN 194310	Synthetic	pan-RAR	None	Oral	Preclinical	Acutely toxic
RAR antagonist	BMS-189453	Synthetic	pan-RAR	None	Oral	Preclinical	Acutely toxic
RAR antagonist	LY2955303	Synthetic	RARγ	None	Oral	Preclinical	Acutely toxic
RAR antagonist	YCT529	Synthetic	RARα	None	Oral	Phase I	Unknown

Category	Compound	Type	Receptor specificity	FDA approval	Route	Highest stage	Known adverse events
RAR agonist	Tretinoin	Natural	RARα/β/γ	APL	Oral	FDA approved	L T R B D
RAR agonist	Palovarotene	Synthetic	RARγ	Fibrodysplasia ossificans progressiva	Oral	FDA approved	D B
RAR agonist	Tamibarotene (Am80)	Synthetic	RARα	None	Oral	Phase III	L T R B D
RAR agonist	Fenretinide	Synthetic	RARα/β/γ	None	Oral	Phase III	L D V I
RAR agonist	IRX5183	Synthetic	RARα	None	Oral	Phase II	L I
RAR agonist	Amsilarotene (TAC-101)	Synthetic	RARα	None	Oral	Phase II	L
RAR agonist	Trifarotene	Synthetic	RARγ	Acne vulgaris	Topical	FDA approved	Mild D
RAR agonist	Adapalene	Synthetic	RARβ/γ	Acne vulgaris	Topical	FDA approved	Mild D
RAR agonist	Tazarotene	Synthetic	RARβ/γ	Acne vulgaris/psoriasis	Topical	FDA approved	D T
RAR agonist	Alitretinoin (9-cis RA)	Natural	RXRα/β/γ	Cutaneous Kaposi sarcoma	Topical	FDA approved	D
RXR agonist	Bexarotene	Synthetic	RXRα/β/γ	CTCL	Oral	FDA approved	L T D V H
Non-nuclear pathway	Isotretinoin (Accutane, 13-cis RA)	Natural	None	Acne vulgaris	Oral	FDA approved	D V N B
RA biosynthesis	Disulfiram	Synthetic	ALDH1a1/2 inhibitor	Alcohol aversion	Oral	FDA approved	I
RA biosynthesis	WIN18446	Synthetic	ALDH1a1,2,3	None	Oral	Phase I	Male infertility
RA biosynthesis	Talarazole	Synthetic	Cyp26 inhibitor	None	Oral	Phase II	Acutely toxic
RAR antagonist	AGN 194310	Synthetic	pan-RAR	None	Oral	Preclinical	Acutely toxic
RAR antagonist	BMS-189453	Synthetic	pan-RAR	None	Oral	Preclinical	Acutely toxic
RAR antagonist	LY2955303	Synthetic	RARγ	None	Oral	Preclinical	Acutely toxic
RAR antagonist	YCT529	Synthetic	RARα	None	Oral	Phase I	Unknown

Acitretin is not included due to unknown mechanism of action. Key for known adverse events: L: hyperlipidemia; T: teratogenic (where known); R: retinoic acid syndrome; B: bone or muscle pain; D: dermatologic symptoms such as rash; V: vision effects; I: liver damage; N: neurological symptoms; H: hypothyroidism.

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