Table 1.
TYK2 inhibitors under development that have advanced to phase 2 and 3 clinical trials.
| Inhibitor type | Name | Selectivity | Kinase inhibition IC50 (uM) |
Phase 3–4 clinical trials | Phase 2 clinical trials |
|---|---|---|---|---|---|
| Allosteric (JH2) | Deucravacitinib BMS-986165 Approved for treatment of psoriasis FDA 2022 |
TYK2 JH2 | JAK1: >10,000 JAK2: >10,000 JAK3: >10,000 TYK2 (JH1): >10,000 TYK2 (JH2): 0.2 nM |
Psoriasis (NCT04772079, NCT05702995, NCT05478499, NCT004036435, NCT03611751, NCT03624127, NCT03924427, NCT04167462, NCT05478499, NCT05701995) Palmoplantar postulosis (NCT05710185) Systemic lupus erythematosus (NCT05617677, NCT05620407) Psoriatic arthritis (NCT04908202, NCT04908189) |
Alopecia areata (NCT05556265, NCT03252587) Lupus erythematosus discoid/subacute cutaneous (NCT04857034) Lupus nephritis (NCT03943147) Ulcerative colitis (NCT03934216, NCT04613518, NCT04877990) Crohn's disease (NCT04877990, NCT03599622) |
| NDI-034858 TAK-279 | TYK2 JH2 | Psoriatic arthritis (NCT05153148) Psoriasis (NCT04999839) |
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| VTX958 | TYK2 JH2 | Psoriasis (NCT05655299) Crohn's disease (NCT05688852) Psoriatic arthritis (NCT05715125) |
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| ESK-001 | TYK2 JH2 | Psoriasis (NCT05739435, NCT05600036) | |||
| BMS-986202 | TYK2 JH2 | TYK2 JH2: 0.19 nM | None | None | |
| ATP competitive (JH1) | Ropsacitinib PF-06826647 | TYK2 (>JAK2 > JAK1) | JAK1: 383 nM JAK2: 74 nM JAK3: >10,000 nM TYK2: 17 nM |
None | Psoriasis (NCT03895372) Ulcerative colitis (NCT04209556 withdrawn) Hidradenitis suppurativa (NCT04092452) |
| SAR-20347 | TYK2(>JAK1 > JAK2 > JAK3) | JAK1: 23 nM JAK2: 26 nM JAK3: 41 nM TYK2: 0.6 nM |
None | None | |
| NDI-031407 | TYK2(>JAK3 > JAK2 > JAK1) | JAK1: 46 nM JAK2: 31 nM JAK3: 4.2 nM TYK2: 0.21 nM |
None | None | |
| GLPG3667 | TYK2 | None | Dermatomyositis (NCT05695950) | ||
| ATP competitive (JH1) dual | Brepocitinib PF-06700841 | JAK1, TYK2 (>JAK2) | JAK1: 17 nM JAK2: 77 nM JAK3: 6494 nM TYK2: 23 nM |
Dermatomyositis (NCT05437263) | Cicatricial alopecia (NCT05076006, NCT05076006) Atopic dermatitis (NCT03903822) Systemic lupus erythematosus (NCT03845517) Psoriatic arthritis (NCT03963401) Psoriasis (NCT02969018, NCT03850483) Crohn's disease (NCT03395184) Ulcerative colitis (NCT02958865) Alopecia areata (NCT02974868) Hidradenitis suppurativa (NCT04092452) Vitiligo (NCT03715829) Uveitis (NCT05523765) |
| TLL018 | JAK1/TYK2 | JAK1: 4 nM JAK2: >1000 nM JAK3: >1000 nM TYK2: 5 nM |
None | Ulcerative colitis (NCT05121402) withdrawn Rheumatoid arthritis (NCT05133297) |
|
| ATP competitive (JH1) tissue restricted | OST-122 | JAK3/TYK2/ARK5 gut-selective | None | Ulcerative colitis (NCT04353791) |
Only trials of the highest phase number are included.