解説ページ「GPCRについて」に示したように、医薬品標的としての開発度合いはそれぞれのGPCRで大きく異なります。一部のGPCRには市販薬が何十もある一方、大多数のGPCRには承認薬も開発薬もないまま取り残されています。
GPCR薬データベース [1,2] を集計し標的薬の数の多い順にGPCRを並べました(図は昇順、表は降順)。受容体による偏りが大きいことが一目瞭然です。なお、このランキングの圏外にも創薬が手がけられていない約150種の非感覚GPCRが存在します。
化合物と受容体の組み合わせのうちデータベース [1] に複数の開発段階(例えば Approved と Phase 3)が登録されているものについては、最も進んだ段階を採用しました。また、Withdrawn は Phase 3 と Approved の中間と見なしました。Withdrawn された薬は一度は承認審査を通過したという点で Phase 3 より進んでいて、時の試練に耐えなかったという点で今でも承認されている薬ほどには進んでいないという理屈です。
| Rank | Target | Total | Approved | Withdrawn | Phase 3 | Phase 2 | Phase 1 | Preclinical |
|---|---|---|---|---|---|---|---|---|
| 1 | DRD2 | 85 | 61 | 1 | 11 | 7 | 5 | 0 |
| 2 | HRH1 | 79 | 73 | 1 | 2 | 3 | 0 | 0 |
| 3 | 5HT2A | 70 | 43 | 1 | 10 | 12 | 4 | 0 |
| 4 | ACM1 | 63 | 55 | 1 | 0 | 3 | 4 | 0 |
| 5 | ADRB2 | 62 | 43 | 0 | 1 | 16 | 2 | 0 |
| 6 | ADA1A | 60 | 53 | 1 | 1 | 5 | 0 | 0 |
| 7 | OPRM | 55 | 39 | 0 | 7 | 5 | 4 | 0 |
| 8 | ACM3 | 50 | 40 | 1 | 2 | 6 | 1 | 0 |
| 9 | ACM2 | 44 | 39 | 1 | 0 | 3 | 1 | 0 |
| 10 | ADA1B | 42 | 38 | 1 | 0 | 3 | 0 | 0 |
| 11 | ADRB1 | 42 | 38 | 0 | 0 | 4 | 0 | 0 |
| 12 | ADA2A | 41 | 34 | 0 | 2 | 4 | 0 | 1 |
| 13 | 5HT1A | 38 | 23 | 0 | 6 | 8 | 1 | 0 |
| 14 | ADA2B | 37 | 30 | 0 | 1 | 4 | 1 | 1 |
| 15 | 5HT2C | 37 | 26 | 1 | 5 | 5 | 0 | 0 |
| 16 | ADA1D | 36 | 32 | 1 | 0 | 3 | 0 | 0 |
| 17 | ADA2C | 36 | 30 | 0 | 1 | 4 | 0 | 1 |
| 18 | DRD3 | 35 | 25 | 0 | 5 | 2 | 2 | 1 |
| 19 | DRD1 | 34 | 28 | 0 | 3 | 1 | 2 | 0 |
| 20 | OPRK | 33 | 19 | 0 | 5 | 6 | 3 | 0 |
| 21 | DRD4 | 29 | 22 | 0 | 4 | 1 | 2 | 0 |
| 22 | OPRD | 29 | 16 | 0 | 4 | 7 | 2 | 0 |
| 23 | GLP1R | 28 | 6 | 0 | 3 | 10 | 9 | 0 |
| 24 | CNR1 | 22 | 4 | 1 | 3 | 8 | 5 | 1 |
| 25 | GNRHR | 20 | 12 | 0 | 3 | 5 | 0 | 0 |
| 26 | ACM4 | 19 | 16 | 1 | 0 | 1 | 1 | 0 |
| 27 | 5HT2B | 19 | 10 | 0 | 4 | 4 | 1 | 0 |
| 28 | 5HT1B | 18 | 13 | 0 | 0 | 4 | 1 | 0 |
| 29 | AA2AR | 18 | 5 | 0 | 6 | 7 | 0 | 0 |
| 30 | ACM5 | 17 | 14 | 1 | 0 | 1 | 1 | 0 |
| 31 | 5HT6R | 17 | 3 | 1 | 3 | 7 | 3 | 0 |
| 32 | AGTR1 | 16 | 9 | 0 | 3 | 4 | 0 | 0 |
| 33 | ADRB3 | 15 | 9 | 0 | 3 | 1 | 2 | 0 |
| 34 | EDNRA | 15 | 4 | 0 | 5 | 6 | 0 | 0 |
| 35 | 5HT1D | 14 | 10 | 0 | 0 | 3 | 1 | 0 |
| 36 | AA1R | 14 | 3 | 0 | 3 | 6 | 2 | 0 |
| 37 | DRD5 | 13 | 9 | 0 | 1 | 1 | 2 | 0 |
| 38 | 5HT4R | 13 | 4 | 0 | 2 | 5 | 2 | 0 |
| 39 | HRH2 | 12 | 12 | 0 | 0 | 0 | 0 | 0 |
| 40 | CNR2 | 12 | 3 | 0 | 1 | 5 | 1 | 2 |
| 41 | PD2R2 | 12 | 1 | 0 | 2 | 6 | 3 | 0 |
| 42 | NK1R | 11 | 3 | 0 | 1 | 6 | 1 | 0 |
| 43 | CXCR4 | 11 | 1 | 0 | 2 | 5 | 3 | 0 |
| 44 | 5HT7R | 10 | 7 | 0 | 2 | 1 | 0 | 0 |
| 45 | P2Y12 | 10 | 6 | 0 | 0 | 3 | 1 | 0 |
| 46 | V2R | 10 | 5 | 0 | 2 | 3 | 0 | 0 |
| 47 | SSR2 | 10 | 4 | 0 | 0 | 3 | 3 | 0 |
| 48 | S1PR1 | 10 | 2 | 0 | 3 | 3 | 2 | 0 |
| 49 | GRM5 | 10 | 1 | 0 | 1 | 8 | 0 | 0 |
| 50 | HRH3 | 9 | 1 | 0 | 1 | 4 | 3 | 0 |
| 51 | PI2R | 8 | 5 | 0 | 1 | 2 | 0 | 0 |
| 52 | V1AR | 8 | 4 | 0 | 1 | 2 | 1 | 0 |
| 53 | GABR1 | 8 | 4 | 0 | 1 | 1 | 1 | 1 |
| 54 | SSR5 | 8 | 4 | 0 | 0 | 3 | 1 | 0 |
| 55 | SMO | 8 | 3 | 0 | 0 | 3 | 2 | 0 |
| 56 | CCR2 | 8 | 0 | 0 | 1 | 4 | 3 | 0 |
| 57 | LSHR | 7 | 5 | 0 | 0 | 1 | 1 | 0 |
| 58 | EDNRB | 7 | 3 | 0 | 2 | 2 | 0 | 0 |
| 59 | PTH1R | 7 | 3 | 0 | 1 | 3 | 0 | 0 |
| 60 | OXYR | 7 | 2 | 0 | 3 | 2 | 0 | 0 |
| 61 | AA3R | 7 | 2 | 0 | 2 | 2 | 1 | 0 |
| 62 | GLR | 7 | 1 | 0 | 0 | 4 | 2 | 0 |
| 63 | MSHR | 7 | 0 | 0 | 2 | 2 | 2 | 1 |
| 64 | CXCR2 | 7 | 0 | 0 | 1 | 4 | 2 | 0 |
| 65 | PE2R1 | 6 | 5 | 0 | 0 | 0 | 1 | 0 |
| 66 | FSHR | 6 | 4 | 0 | 1 | 1 | 0 | 0 |
| 67 | PF2R | 6 | 4 | 0 | 1 | 0 | 1 | 0 |
| 68 | AA2BR | 6 | 4 | 0 | 0 | 1 | 1 | 0 |
| 69 | HCAR2 | 6 | 3 | 0 | 0 | 2 | 1 | 0 |
| 70 | SSR1 | 6 | 3 | 0 | 0 | 2 | 1 | 0 |
| 71 | CASR | 6 | 2 | 0 | 1 | 2 | 0 | 1 |
| 72 | GABR2 | 6 | 2 | 0 | 1 | 1 | 1 | 1 |
| 73 | CCR5 | 6 | 1 | 0 | 4 | 1 | 0 | 0 |
| 74 | OX2R | 6 | 1 | 0 | 1 | 4 | 0 | 0 |
| 75 | OX1R | 6 | 1 | 0 | 1 | 3 | 1 | 0 |
| 76 | CALRL | 6 | 0 | 0 | 3 | 3 | 0 | 0 |
| 77 | GHSR | 6 | 0 | 0 | 2 | 3 | 1 | 0 |
| 78 | GRM2 | 6 | 0 | 0 | 2 | 2 | 2 | 0 |
| 79 | 5HT1F | 5 | 4 | 0 | 1 | 0 | 0 | 0 |
| 80 | MTR1A | 5 | 4 | 0 | 0 | 1 | 0 | 0 |
| 81 | MTR1B | 5 | 4 | 0 | 0 | 1 | 0 | 0 |
| 82 | CLTR1 | 5 | 4 | 0 | 0 | 0 | 1 | 0 |
| 83 | PE2R3 | 5 | 3 | 0 | 0 | 1 | 1 | 0 |
| 84 | P2RY2 | 5 | 1 | 0 | 3 | 1 | 0 | 0 |
| 85 | CRFR1 | 5 | 1 | 0 | 2 | 2 | 0 | 0 |
| 86 | MC4R | 5 | 0 | 0 | 2 | 1 | 2 | 0 |
| 87 | GRM3 | 5 | 0 | 0 | 2 | 1 | 2 | 0 |
| 88 | TAAR1 | 4 | 3 | 0 | 0 | 1 | 0 | 0 |
| 89 | CALCR | 4 | 3 | 0 | 0 | 1 | 0 | 0 |
| 90 | V1BR | 4 | 3 | 0 | 0 | 1 | 0 | 0 |
| 91 | PE2R2 | 4 | 3 | 0 | 0 | 0 | 1 | 0 |
| 92 | GHRHR | 4 | 2 | 0 | 0 | 2 | 0 | 0 |
| 93 | PTH2R | 4 | 1 | 0 | 1 | 2 | 0 | 0 |
| 94 | HCAR3 | 4 | 1 | 0 | 0 | 2 | 1 | 0 |
| 95 | CCR9 | 4 | 0 | 0 | 2 | 0 | 2 | 0 |
| 96 | HRH4 | 4 | 0 | 0 | 1 | 3 | 0 | 0 |
| 97 | AGTR2 | 4 | 0 | 0 | 1 | 2 | 1 | 0 |
| 98 | CXCR1 | 4 | 0 | 0 | 1 | 2 | 1 | 0 |
| 99 | GPR55 | 4 | 0 | 0 | 1 | 2 | 0 | 1 |
| 100 | GP119 | 4 | 0 | 0 | 0 | 2 | 2 | 0 |
| 101 | SSR3 | 3 | 2 | 0 | 0 | 0 | 1 | 0 |
| 102 | PAR1 | 3 | 1 | 0 | 1 | 1 | 0 | 0 |
| 103 | FFAR1 | 3 | 1 | 0 | 1 | 0 | 1 | 0 |
| 104 | GLP2R | 3 | 1 | 0 | 0 | 2 | 0 | 0 |
| 105 | PE2R4 | 3 | 1 | 0 | 0 | 1 | 1 | 0 |
| 106 | SSR4 | 3 | 1 | 0 | 0 | 1 | 1 | 0 |
| 107 | MC3R | 3 | 0 | 0 | 1 | 2 | 0 | 0 |
| 108 | PD2R | 3 | 0 | 0 | 1 | 1 | 1 | 0 |
| 109 | MTLR | 3 | 0 | 0 | 0 | 2 | 1 | 0 |
| 110 | CCKAR | 2 | 0 | 1 | 1 | 0 | 0 | 0 |
| 111 | SCTR | 2 | 1 | 0 | 1 | 0 | 0 | 0 |
| 112 | GPR35 | 2 | 1 | 0 | 0 | 1 | 0 | 0 |
| 113 | BKRB2 | 2 | 1 | 0 | 0 | 1 | 0 | 0 |
| 114 | GASR | 2 | 1 | 0 | 0 | 1 | 0 | 0 |
| 115 | TA2R | 2 | 1 | 0 | 0 | 1 | 0 | 0 |
| 116 | OPRX | 2 | 0 | 0 | 1 | 1 | 0 | 0 |
| 117 | P2RY1 | 2 | 0 | 0 | 1 | 1 | 0 | 0 |
| 118 | P2RY4 | 2 | 0 | 0 | 1 | 1 | 0 | 0 |
| 119 | P2Y11 | 2 | 0 | 0 | 1 | 1 | 0 | 0 |
| 120 | P2Y13 | 2 | 0 | 0 | 1 | 1 | 0 | 0 |
| 121 | P2Y14 | 2 | 0 | 0 | 1 | 1 | 0 | 0 |
| 122 | P2RY8 | 2 | 0 | 0 | 1 | 1 | 0 | 0 |
| 123 | P2Y10 | 2 | 0 | 0 | 1 | 1 | 0 | 0 |
| 124 | CRFR2 | 2 | 0 | 0 | 1 | 1 | 0 | 0 |
| 125 | VIPR2 | 2 | 0 | 0 | 1 | 1 | 0 | 0 |
| 126 | LPAR4 | 2 | 0 | 0 | 1 | 1 | 0 | 0 |
| 127 | LPAR6 | 2 | 0 | 0 | 1 | 1 | 0 | 0 |
| 128 | C5AR1 | 2 | 0 | 0 | 1 | 0 | 1 | 0 |
| 129 | GRM4 | 2 | 0 | 0 | 1 | 0 | 1 | 0 |
| 130 | LT4R1 | 2 | 0 | 0 | 0 | 2 | 0 | 0 |
| 131 | NK3R | 2 | 0 | 0 | 0 | 2 | 0 | 0 |
| 132 | NPY4R | 2 | 0 | 0 | 0 | 2 | 0 | 0 |
| 133 | CML1 | 2 | 0 | 0 | 0 | 1 | 1 | 0 |
| 134 | P2RY6 | 2 | 0 | 0 | 0 | 1 | 1 | 0 |
| 135 | NPY2R | 2 | 0 | 0 | 0 | 1 | 1 | 0 |
| 136 | LGR5 | 2 | 0 | 0 | 0 | 0 | 2 | 0 |
| 137 | 5HT5A | 1 | 1 | 0 | 0 | 0 | 0 | 0 |
| 138 | ACTHR | 1 | 1 | 0 | 0 | 0 | 0 | 0 |
| 139 | S1PR5 | 1 | 1 | 0 | 0 | 0 | 0 | 0 |
| 140 | NTR2 | 1 | 1 | 0 | 0 | 0 | 0 | 0 |
| 141 | CLTR2 | 1 | 1 | 0 | 0 | 0 | 0 | 0 |
| 142 | TRFR | 1 | 1 | 0 | 0 | 0 | 0 | 0 |
| 143 | PTAFR | 1 | 1 | 0 | 0 | 0 | 0 | 0 |
| 144 | TSHR | 1 | 1 | 0 | 0 | 0 | 0 | 0 |
| 145 | BKRB1 | 1 | 1 | 0 | 0 | 0 | 0 | 0 |
| 146 | 5HT1E | 1 | 1 | 0 | 0 | 0 | 0 | 0 |
| 147 | GRM6 | 1 | 0 | 0 | 1 | 0 | 0 | 0 |
| 148 | GRM7 | 1 | 0 | 0 | 1 | 0 | 0 | 0 |
| 149 | GRM8 | 1 | 0 | 0 | 1 | 0 | 0 | 0 |
| 150 | CCR4 | 1 | 0 | 0 | 1 | 0 | 0 | 0 |
| 151 | PAR3 | 1 | 0 | 0 | 1 | 0 | 0 | 0 |
| 152 | PAR4 | 1 | 0 | 0 | 1 | 0 | 0 | 0 |
| 153 | NK2R | 1 | 0 | 0 | 1 | 0 | 0 | 0 |
| 154 | RXFP1 | 1 | 0 | 0 | 1 | 0 | 0 | 0 |
| 155 | RXFP2 | 1 | 0 | 0 | 1 | 0 | 0 | 0 |
| 156 | VIPR1 | 1 | 0 | 0 | 1 | 0 | 0 | 0 |
| 157 | GRM1 | 1 | 0 | 0 | 1 | 0 | 0 | 0 |
| 158 | LPAR1 | 1 | 0 | 0 | 0 | 1 | 0 | 0 |
| 159 | MC5R | 1 | 0 | 0 | 0 | 1 | 0 | 0 |
| 160 | CCR1 | 1 | 0 | 0 | 0 | 1 | 0 | 0 |
| 161 | FFAR2 | 1 | 0 | 0 | 0 | 1 | 0 | 0 |
| 162 | GPR84 | 1 | 0 | 0 | 0 | 1 | 0 | 0 |
| 163 | MCHR1 | 1 | 0 | 0 | 0 | 1 | 0 | 0 |
| 164 | CCR3 | 1 | 0 | 0 | 0 | 1 | 0 | 0 |
| 165 | MAS | 1 | 0 | 0 | 0 | 1 | 0 | 0 |
| 166 | NPY5R | 1 | 0 | 0 | 0 | 1 | 0 | 0 |
| 167 | APJ | 1 | 0 | 0 | 0 | 0 | 1 | 0 |
| 168 | CX3C1 | 1 | 0 | 0 | 0 | 0 | 1 | 0 |
| 169 | GPBAR | 1 | 0 | 0 | 0 | 0 | 1 | 0 |
| 170 | FZD8 | 1 | 0 | 0 | 0 | 0 | 1 | 0 |
| 171 | GIPR | 1 | 0 | 0 | 0 | 0 | 1 | 0 |
| 172 | LGR4 | 1 | 0 | 0 | 0 | 0 | 1 | 0 |
| 173 | FZD10 | 1 | 0 | 0 | 0 | 0 | 1 | 0 |
| 174 | FZD7 | 1 | 0 | 0 | 0 | 0 | 1 | 0 |
References
- DrugBrowser. GPCRdb. https://gpcrdb.org/drugs/drugbrowser (accessed December 6, 2019).
- Hauser AS, Attwood MM, Rask-Andersen M, Schiöth HB, Gloriam DE. Trends in GPCR drug discovery: new agents, targets and indications. Nat Rev Drug Discov. 2017;16:829-842.
