The CTP of innovative targets of first-in-class small molecule drugs approved in 2004–17. The progression timeline of each target is from the year of 1st phase I to the year of 1st drug approval. The name of the 1st approved drug and the corresponding disease indication are provided. Clinical trial or approval status of each year is represented as follows: phase I (light blue square), phase II (light green square), phase III (yellow square) and the 1st small molecule drug approval (light orange tablet). The number (n) in each square indicates the number of clinical trial drugs of all phases in each specific year, the question mark (?) inside the squares is a putatively estimated earlier trial phase and the letter `c’ inside the squares denotes that a completion of a trial phase reported in that year. Abbreviations for target: ADRB3, Beta 3 adrenoceptor; Alk, ALK tyrosine kinase receptor; BCL-2, Apoptosis regulator Bcl-2; BRaf, proto-oncogene B-Raf; Btk, Btk tyrosine kinase; CCR5, CC-chemokine receptor 5; CDK4/6, cyclin-dependent kinase-4/6; CFTR, cystic fibrosis transmembrane conductance regulator; CLCN2, chloride channel protein 2; CPS1, carbamoyl phosphate synthetase 1; CXCR4, C-X-C chemokine receptor type 4; CYP17A1, cytochrome P450 17A1; CaSR, extracellular calcium sensing receptor; DPP4, dipeptidyl peptidase IV; FXR, Farnesoid X receptor; HCN channel, hyperpolarization-activated cyclic nucleotide-gated channel; HDAC, histone deacetylase; IDH2, isocitrate dehydrogenase 2; Jak2, Jak2 tyrosine kinase; Jak3, Jak3 tyrosine kinase; LFA-1, lymphocyte function-associated antigen-1; MEK, MEK protein kinase; MT1/2 receptor, melatonin MT1/2 receptor; Orexin receptor, OX1/2 orexin receptor; PAH, phenylalanine hydroxylase; PAR-1, protease-activated receptor-1; PARP, poly ADP ribose polymerase; PDE-4, phosphodiesterase 4; PI3K delta, phosphoinositide-3 kinase delta; ROCK, rho kinase; Ret, Ret tyrosine kinase receptor; S1PR1, sphingosine 1-phosphate receptor 1; SC5A2, sodium glucose transporter-2; sGC, soluble guanylyl cyclase; TPH, tryptophan hydroxylase; Transfer protein MTP, microsomal triglyceride transfer protein; VEGFR2, VEGF-2 receptor. Abbreviation for disease: AML, acute myeloid leukemia; BCC, basal cell carcinoma; CIC, chronic idiopathic constipation; CLL, chronic lymphocytic leukemia; COPD, chronic obstructive pulmonary disease; CTCL, cutaneous T-cell lymphoma; CTEPH, chronic thromboembolic pulmonary hypertension; DACS, diarrhea associated with carcinoid syndrome; DED, dry eye disease; FH, familial hypercholesterolemia; FL, follicular lymphoma; HPA, hyperphenylalaninemia; “”MCL, mantle cell lymphoma; MI, myocardial infarction; MM, multiple myeloma; MTC, medullary thyroid cancer; NHL, non-Hodgkin lymphoma; NSCLC, non-small-cell lung carcinoma; PAD, peripheral arterial disease; PAH, pulmonary arterial hypertension; PB,: primary biliary cholangitis; RCC, renal cell carcinoma; SHP,: secondary hyperparathyroidism; SLL, small lymphocytic lymphoma.