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. 2019 Jan 23;21(2):649–662. doi: 10.1093/bib/bby130

Figure 4.

Figure 4

The CTP of the innovative targets of the first-in-class drugs approved in 2004–17 for treating cancers (Cancer) and diseases of musculoskeletal system and connective tissue (Bone). The progression timeline of each target is from the year of 1st phase I to the year of the 1st drug approval. The name of the 1st approved drug and the corresponding disease indications are provided. The 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 drug approval (light orange tablet, blue capsule and violet red tablet for small molecule, antibody and protein drug, respectively). 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 indicates the putatively estimated earlier trial phase and the letter `c’ inside the squares denotes that a completion of a trial phase reported in that year. Abbreviation for target: Alk, ALK tyrosine kinase receptor; BCL-2, apoptosis regulator Bcl-2; BLyS ligand, B-lymphocyte stimulator ligand; BRaf, proto-oncogene B-Raf; Btk, Btk tyrosine kinase; CD19, B-lymphocyte antigen CD19; CD38, cADPr hydrolase 1; CDK4/6, cyclin-dependent kinase-4/6; CTLA-4, cytotoxic T-lymphocyte protein-4; CXCR4, C-X-C chemokine receptor type 4; CYP17A1, cytochrome P450 17A1; HDAC, histone deacetylase; IDH2, isocitrate dehydrogenase 2; IL-6, interleukin-6 ligand; IL-6R, interleukin-6 receptor; Jak2, Jak2 tyrosine kinase; Jak3, Jak3 tyrosine kinase; MEK, MEK protein kinase; PARP, poly ADP ribose polymerase; PD-1, programmed cell death protein 1; PI3K delta, phosphoinositide-3 kinase delta; RANKL, receptor activator of nuclear factor kappa-B ligand; Ret, Ret tyrosine kinase receptor; SLAMF7, SLAM family member 7; VEGF-A, VEGF-A ligand; VEGFR2, VEGF-2 receptor. Abbreviation for disease (class): AML: acute myeloid leukemia; B-ALL, B-cell precursor acute lymphoblastic leukemia; BCC, basal cell carcinoma; CLL, chronic lymphocytic leukemia; CRC, colorectal cancer; CTCL, Cutaneous T cell lymphoma; FL, Follicular lymphoma; MCD, multicentric Castleman disease; MCL, mantle cell lymphoma; MM, multiple myeloma; MTC, medullary thyroid cancer; NHL, non-Hodgkin lymphoma; NSCLC, non-small-cell lung carcinoma; RCC, renal cell carcinoma; SLE, systemic lupus erythematosus; SLL, small lymphocytic lymphoma.