In one aspect, the present disclosure provides tubulysin analogs of the formula (I) wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4, X.sub.1, X.sub.2, X.sub.3, and A.sub.1 are as defined herein. In another aspect, the present disclosure also provides methods of preparing the compounds disclosed herein. In another aspect, the present disclosure also provides pharmaceutical compositions and methods of use of the compounds disclosed herein.

##STR00001##

Provided herein are compounds, compositions, and methods for the treatment of diseases and disorders associated with cancer, including tubulysins and protein (e.g., antibody) drug conjugates thereof.

Described herein are compounds, pharmaceutical compositions and methods for treating pathogenic cell populations. The compounds described herein include conjugates of tubulysins and vitamin receptor binding ligands. The conjugates also include a releasable bivalent linker.

The invention described herein pertains to the diagnosis, imaging, and/or treatment of pathogenic cell populations. In particular, the invention described herein pertains to the diagnosis, imaging, and/or treatment of diseases caused by PSMA expressing cells, such as prostate cancer cells, using compounds capable of targeting PSMA expressing cells.

The invention described herein pertains to the diagnosis, imaging, and/or treatment of pathogenic cell populations. In particular, the invention described herein pertains to the diagnosis, imaging, and/or treatment of diseases caused by PSMA expressing cells, such as prostate cancer cells, using compounds capable of targeting PSMA expressing cells.

The invention described herein pertains to the diagnosis, imaging, and/or treatment of pathogenic cell populations. In particular, the invention described herein pertains to the diagnosis, imaging, and/or treatment of diseases caused by PSMA expressing cells, such as prostate cancer cells, using compounds capable of targeting PSMA expressing cells.

The presently disclosed inventive concept(s) include inhibitors of antiplasmin cleaving enzyme (APCE) and fibroblast activation protein alpha (FAP) which can be used in various therapies related to disorders of fibrin and .sub.2-antiplasmin and abnormal cell proliferation. The presently disclosed inventive concept(s) also include substrates of APCE and FAP, which may be used, for example, in screening methods for identifying such inhibitors. The presently disclosed inventive concept(s) further include, but are not limited to, methods of treating or inhibiting atherosclerosis and thrombus disorders by altering the ratios of types of plasma .sub.2-antiplasmin and to methods of treating conditions involving abnormal cell proliferation such as cancers.

Antiproliferative compounds having a structure represented by formula (II), where n, R.sup.1, R.sup.2, R.sup.3, R.sup.4, and R.sup.5 are as defined herein, can be used to treat tumors, optionally when conjugated to a ligand such as an antibody: ##STR00001##

Small molecule, peptidic hepatocyte growth factors mimics, which act as both mimetics and antagonists, have been generated. These molecules have been shown or predicted to have therapeutic potential for numerous pathologies including dementia, neurodegenerative disease, diabetes and metabolic syndrome, cancer, and defective wound healing.

Described herein are compounds, pharmaceutical compositions and methods for treating pathogenic cell populations. The compounds described herein include conjugates of tubulysins and vitamin receptor binding ligands. The conjugates also include a releasable bivalent linker.