Engineered non-plant cells that produce a benzylisoquinoline alkaloid product that is a derivative of canadine along a metabolic pathway that converts canadine, or an analog of canadine, to a noscapinoid product are provided. Methods of culturing engineered non-plant cells that produce a noscapinoid product and pharmaceutical compositions are also provided.

Engineered non-plant cells that produce a benzylisoquinoline alkaloid product that is a derivative of canadine along a metabolic pathway that converts canadine, or an analog of canadine, to a noscapinoid product are provided. Methods of culturing engineered non-plant cells that produce a noscapinoid product and pharmaceutical compositions are also provided.

The present application discloses compounds of Formula (I). Such compounds, pharmaceutically acceptable salts and compositions thereof, are inhibitors of Mcl-1 proteins and are useful in treating diseases and conditions characterized by excessive cellular proliferation such as cancer.

##STR00001##

The present application discloses compounds of Formula (I). Such compounds, pharmaceutically acceptable salts and compositions thereof, are inhibitors of Mcl-1 proteins and are useful in treating diseases and conditions characterized by excessive cellular proliferation such as cancer.

##STR00001##

Disclosed is a compound which is 17-chloro-5,13,14,22-tetramethyl-28-oxa-2,9-dithia-5,6,12,13,22-pentaazaheptacyclo[27.7.1.1.sup.4,7.0.sup.11,15.0.sup.16,21.0.sup.20,24.0.sup.30,35]octatriaconta-1(37),4(38),6,11,14,16,18,20,23,29,31,33,35-tridecaene-23-carboxylic acid (Formula I)

##STR00001##

and enantiomers and pharmaceutically acceptable salts thereof. Also disclosed are pharmaceutical compositions of 17-chloro-5,13,14,22-tetramethyl-28-oxa-2,9-dithia-5,6,12,13,22-pentaazaheptacyclo[27.7.1.1.sup.4,7.0.sup.11,15.0.sup.16,21.0.sup.20,24.0.sup.30,35]octatriaconta-1(37),4(38),6,11,14,16,18,20,23,29,31,33,35-tridecaene-23-carboxylic acid, and enantiomers and pharmaceutically acceptable salts thereof, and methods of treating cancer with such compounds and compositions.

The present invention relates to pharmaceutical agents useful for therapy and/or prophylaxis in a subject, pharmaceutical composition comprising such compounds, and their use as MCL-1 inhibitors, useful for treating diseases such as cancer.

##STR00001##

The present invention relates to pharmaceutical agents useful for therapy and/or prophylaxis in a subject, pharmaceutical composition comprising such compounds, and their use as MCL-1 inhibitors, useful for treating diseases such as cancer.

##STR00001##

There is provided compounds of formula I, wherein R1, R.sup.2a, R.sup.2b, R.sup.2c, X, Y, Z, R.sup.3 and ring A/B have meanings given in the description, and pharmaceutically-acceptable esters, amides, solvates or salts thereof, which compounds are useful in the treatment of diseases in which inhibition of a protein or lipid kinase (e.g. PI3-K, particularly class I PI3K, PIM family kinase and/or mTOR) is desired and/or required, and particularly in the treatment of cancer. The invention also relates to combinations containing such compounds. ##STR00001##

There is provided compounds of formula I, wherein R1, R.sup.2a, R.sup.2b, R.sup.2c, X, Y, Z, R.sup.3 and ring A/B have meanings given in the description, and pharmaceutically-acceptable esters, amides, solvates or salts thereof, which compounds are useful in the treatment of diseases in which inhibition of a protein or lipid kinase (e.g. PI3-K, particularly class I PI3K, PIM family kinase and/or mTOR) is desired and/or required, and particularly in the treatment of cancer. The invention also relates to combinations containing such compounds. ##STR00001##

The present invention relates to an indole macrocyclic derivative, a preparation method therefor and an application thereof in medicine. Specifically, the present invention relates to an indole macrocyclic derivative represented by general formula (IM), a preparation method therefor, a pharmaceutical composition containing the derivative, and a use thereof as a therapeutic agent, especially as an MCL-1 inhibitor. Each substituent of general formula (IM) is the same as those defined in the description.

##STR00001##