Selinexor (KPT-330) is a first in class XPO1 antagonist being evaluated in multiple later stage clinical trials in patients with relapsed and/or refractory hematological and solid tumor malignancies.

Trans-1-amino-3-[(18)F]fluorocyclobutanecarboxylic acid (also known as Fluciclovine (18F)) was approved under brand name AXUMIN as a radioactive diagnostic agent indicated for positron emission tomography (PET) imaging in men with suspected prostate cancer recurrence. Besides, this radioactive compound is used in patients with cervical, ovarian epithelial or endometrial cancers. Fluciclovine F 18 is a synthetic amino acid transported across mammalian cell membranes by amino acid transporters, such as LAT-1 and ASCT2, which are upregulated in prostate cancer cells, but as was shown, this compound has a higher affinity for ASCT2 in comparison with other transporters.

Medroxyprogesterone acetate (INN, USAN, BAN), also known as 17α-hydroxy-6α-methylprogesterone acetate, and commonly abbreviated as MPA, is a steroidal progestin, a synthetic variant of the human hormone progesterone. Medroxyprogesterone acetate (MPA) administered orally or parenterally in the recommended doses to women with adequate endogenous estrogen, transforms proliferative into secretory endometrium. Androgenic and anabolic effects have been noted, but the drug is apparently devoid of significant estrogenic activity. While parenterally administered MPA inhibits gonadotropin production, which in turn prevents follicular maturation and ovulation, available data indicate that this does not occur when the usually recommended oral dosage is given as single daily doses. MPA is a more potent derivative of its parent compound medroxyprogesterone (MP). While medroxyprogesterone is sometimes used as a synonym for medroxyprogesterone acetate, what is normally being administered is MPA and not MP. Used as a contraceptive and to treat secondary amenorrhea, abnormal uterine bleeding, pain associated with endometriosis, endometrial and renal cell carcinomas, paraphilia in males, GnRH-dependent forms of precocious puberty, as well as to prevent endometrial changes associated with estrogens. Progestins diffuse freely into target cells in the female reproductive tract, mammary gland, hypothalamus, and the pituitary and bind to the progesterone receptor. Once bound to the receptor, progestins slow the frequency of release of gonadotropin releasing hormone (GnRH) from the hypothalamus and blunt the pre-ovulatory LH surge.

Estrone, one of the major mammalian estrogens, is an aromatized C18 steroid with a 3-hydroxyl group and a 17-ketone. It is produced in vivo from androstenedione or from testosterone via estradiol. It is produced primarily in the ovaries, placenta, and in peripheral tissues (especially adipose tissue) through conversion of adrostenedione. Estrone may be further metabolized to 16-alpha-hydroxyestrone, which may be reduced to estriol by estradiol dehydrogenase. Estrogens enter the cells of responsive tissues (e.g. female organs, breasts, hypothalamus, pituitary) where they interact with estrogen receptors. Hormone-bound estrogen receptors dimerize, translocate to the nucleus of cells and bind to estrogen response elements (ERE) of genes. Binding to ERE alters the transcription rate of affected genes. Estrogens increase the hepatic synthesis of sex hormone binding globulin (SHBG), thyroid-binding globulin (TBG), and other serum proteins and suppress follicle-stimulating hormone (FSH) release from the anterior pituitary. Estrone dl-Form is a derivative of estrone. As early as 1935 extensive research programs directed toward the total synthesis of the female sex hormone estrone were well under way. These studies have since been continued with increasing interest in laboratories all over the world. In 1942 Bachmann, Kushner and Stevenson succeeded in synthesizing a stereoisomer of the hormone,''estrone a." Using essentially the same synthetic scheme as Bachmann, et al., Anner and Miescher were able to isolate additional stereoisomers including dl-estrone (Estrone, (+-)-Isomer) . Six of the eight possible racemic forms, estrone, a-f, have now been reported. Dl-Estrone (Estrone, (+-)-Isomer) is less active than Estrone.

Gedatolisib (PF-05212384, PKI-587) is a highly potent dual inhibitor of PI3Kα, PI3Kγ and mTOR, originally being developed by Wyeth. Upon intravenous administration, gedatolisib inhibits both PI3K and mTOR kinases, which may result in apoptosis and growth inhibition of cancer cells overexpressing PI3K/mTOR. Activation of the PI3K/mTOR pathway promotes cell growth, survival, and resistance to chemotherapy and radiotherapy; mTOR, a serine/threonine kinase downstream of PI3K, may also be activated independent of PI3K. Significant antitumor efficacy and a favorable pharmacokinetic/safety profile justified clinical evaluation of Gedatolisib. Gedatolisb is in phase II clinical trials by Pfizer for the treatment of acute myeloid leukaemia. Gedatolisb is in phase I clinical trials for the treatment of solid tumours.

Dovitinib is an orally active small molecule that exhibits potent inhibitory activity against multiple receptor tyrosine kinases (RTK) involved in tumor growth and angiogenesis. Dovitinib strongly binds to fibroblast growth factor receptor 3 (FGFR3) and inhibits its phosphorylation, which may result in the inhibition of tumor cell proliferation and the induction of tumor cell death. In addition, this agent may inhibit other members of the RTK superfamily, including the vascular endothelial growth factor receptor; fibroblast growth factor receptor 1; platelet-derived growth factor receptor type 3; FMS-like tyrosine kinase 3; stem cell factor receptor (c-KIT); and colony-stimulating factor receptor 1; this may result in an additional reduction in cellular proliferation and angiogenesis, and the induction of tumor cell apoptosis. There are several ongoing Phase I/III clinical trials for dovitinib.

LY3023414, an investigational drug, is a small molecule that that demonstrates activity against PI3K, mTOR, and DNA-PK in tumor cells, thereby inducing cell-cycle effects and inhibiting cancer cell viability. As shown in vitro LY3023414 inhibits the ability of PI3K and mTOR to phosphorylate substrates in the PI3K/mTOR pathway, one of the most frequently mutated pathways in cancer, leading to cancer progression and resistance to existing treatments. Downstream target inhibition by LY3023414 occurs rapidly via an intermittent “on/off” mechanism that may enhance the drug's clinical tolerability, which may in turn allow LY3023414 to overcome some of the toxicities associated with PI3K/mTOR inhibitors and potentially reduce the emergence of feedback mechanisms leading to resistance. The physicochemical and absorption properties of LY3023414 are favorable, as evidenced by the molecule's high solubility across a wide pH range and high oral bioavailability. On the basis of these findings, LY3023414 is currently being evaluated in clinical trials in patients with advanced cancer such as metastatic prostate cancer and non-small cell lung cancer in combination with other chemotherapeutic agents and in endometrial cancer as a monotherapy.

Uprosertib is an oral potent Akt inhibitor which acts equally on Akt1, Akt2 and Akt3. The drug is under clinical development in combination with trametinib for the treatment of different cancers, including melanoma, myeloma, breast, endometrial, cervical cancer, etc.

Serabelisib (INK1117 and TAK-117) is an orally bioavailable, PI3K p110α- isoform-specific inhibitor with an in vitro IC50 of 15 nM, highly selective against other isoforms (p110β, p110γ, and p110δ) and mTOR (no significant inhibitions at 1 μM concentration). It displayed significant efficacy in several PI3Kα mutant-specific preclinical mouse xenograft tumor models, and blocked signaling to Akt and inhibited the growth of cancer cells harboring wild-type or mutated p110α. Preclinical studies showed TAK-117 to have the low potential for disrupting glucose metabolism or for causing cardiac adverse events; in rats and monkeys, doses up to 50 mg/kg/day were well tolerated. Serabelisib is currently under clinical evaluation.

Apitolisib, a dual inhibitor of mTOR and phosphatidylinositol 3-kinase (PI3K), was being developed by Roche and Genentech as an orally administered therapy of cancer. Apitolisib is a selective, potent, orally bioavailable inhibitor of Class I PI3 kinase (PI3K) and mTOR kinase (TORC1/2) with excellent pharmacokinetic and pharmaceutical properties. Apitolisib displayed excellent potency against class I PI3K isoforms (IC50 PI3K-α, β, δ and γ = 4.8, 27, 6.7 and 14 nM) and mTOR kinase (IC50 = 17 nM) and selectivity against a large panel of other kinases. Apitolisib is in phase II trials by Genentech for the treatment of breast cancer, prostate cancer, endometrium cancer, kidney cancer. However, no recent development has been reported. It is also in phase I trials by Genentech for the treatment of non-Hodgkin's lymphoma.