NPASS Compound

Natural Product: NPC99381

Natural Product ID	NPC99381
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Hypothemycin
IUPAC Name	n.a.
Synonyms	Hypothemycin
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL471474
PubChem CID	9929643
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000147] Macrolides and analogues [CHEMONTID:0001788] Zearalenones

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

Chemical Representations

RDKit 3D 49 51 0 0 0 0 0 0 0 0999 V2000 6.7073 -0.7832 0.4758 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5277 -1.2364 -0.1857 O 0 0 0 0 0 0 0 0 0 0 0 0 4.3331 -0.5543 -0.0099 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2144 -1.0244 -0.6671 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9703 -0.4348 -0.5739 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7795 -0.9889 -1.3020 C 0 0 1 0 0 0 0 0 0 0 0 0 0.8958 -2.3998 -1.3900 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0984 -1.7266 -0.5012 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.4654 -2.1438 -1.0111 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4482 -2.4379 0.0470 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.6491 -3.0175 -0.3320 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.6618 -1.3349 1.0531 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.9900 -2.1234 2.2921 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.8724 -0.5453 0.8364 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9235 -1.1241 1.4796 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.2735 0.6114 0.1831 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6455 1.4739 -0.5375 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2486 1.3245 -0.7947 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3245 2.4959 -0.3163 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.0557 1.8903 -0.6353 O 0 0 0 0 0 0 0 0 0 0 0 0 0.6432 1.3929 0.4242 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2332 1.5100 1.5843 O 0 0 0 0 0 0 0 0 0 0 0 0 1.9047 0.6854 0.2375 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9953 1.1814 0.9072 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2194 0.5632 0.7871 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7958 2.3327 1.7091 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.6058 3.7660 -0.9783 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4709 -0.6372 1.5527 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9833 0.1829 -0.0010 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5165 -1.5237 0.3538 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2749 -1.9161 -1.3111 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5164 -0.5364 -2.2756 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1293 -1.9062 0.5788 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3868 -3.1170 -1.6180 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8683 -1.4376 -1.7890 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9067 -3.2788 0.6949 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9587 -3.5961 0.3921 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7479 -0.8756 1.3321 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1521 -2.6462 2.3911 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3771 0.8815 0.2849 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1805 2.3278 -0.9576 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0371 1.3229 -1.9122 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7945 0.4158 -0.4216 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5137 2.5349 0.7627 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0731 0.9527 1.3116 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1913 3.0523 1.3059 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6286 3.7052 -1.4556 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7053 4.6447 -0.2743 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8557 4.0977 -1.7262 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 10 12 1 0 12 13 1 0 12 14 1 0 14 15 2 0 14 16 1 0 16 17 2 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 2 0 21 23 1 0 23 24 1 0 24 25 2 0 24 26 1 0 19 27 1 0 25 3 1 0 23 5 2 0 8 6 1 0 1 28 1 0 1 29 1 0 1 30 1 0 4 31 1 0 6 32 1 6 8 33 1 1 9 34 1 0 9 35 1 0 10 36 1 1 11 37 1 0 12 38 1 1 13 39 1 0 16 40 1 0 17 41 1 0 18 42 1 0 18 43 1 0 19 44 1 1 25 45 1 0 26 46 1 0 27 47 1 0 27 48 1 0 27 49 1 0 M END

Standard InCHIKey	SSNQAUBBJYCSMY-KNTMUCJRSA-N
Standard InCHI	InChI=1S/C19H22O8/c1-9-4-3-5-12(20)17(23)14(22)8-15-18(27-15)11-6-10(25-2)7-13(21)16(11)19(24)26-9/h3,5-7,9,14-15,17-18,21-23H,4,8H2,1-2H3/b5-3-/t9-,14-,15+,17+,18+/m0/s1
SMILES	COc1cc2[C@H]3O[C@@H]3C[C@H](O)[C@H](O)C(=O)/C=CC[C@@H](OC(=O)c2c(c1)O)C

Calculated Properties

Physi-Chem Properties

MedChem Properties

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

ADMET: Distribution

ADMET: Metabolism

ADMET: Excretion

ADMET: Toxicity

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO14176	Hypomyces subiculosus	Species	Hypocreaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[17067161]
NPO14176	Hypomyces subiculosus	Species	Hypocreaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[20118535]
NPO33691	Paecilomyces sp. SC0930	Species	n.a.	Eukaryota	n.a.	Dinghu Mountain Biosphere Reserve, Guangdong, China	2003-MAR	PMID[28749671]
NPO14176	Hypomyces subiculosus	Species	Hypocreaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO14176	Hypomyces subiculosus	Species	Hypocreaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]

Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

NP Quantity Composition/Concentration

Organism ID	Organism Name	Organism Material Preparation	Organism Part	NP Quantity (Standard)	NP Quantity (Minimum)	NP Quantity (Maximum)	Quantity Unit	Reference

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

Biological Activity

Activity Type	# Activity
IC50	21
Inhibition	13
Activity	1
EC50	1

Activity Type	# Activity
Individual protein	17
Cell line	14
Chimeric protein	1
Organism	3
Unchecked	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT3442	Individual protein	Mitogen-activated protein kinase kinase kinase 7	Homo sapiens	IC50	=	33.0	nM	PMID[26481152]
NPT1650	Individual protein	Tyrosine-protein kinase receptor FLT3	Homo sapiens	Inhibition	=	92.0	%	PMID[30742435]
NPT1650	Individual protein	Tyrosine-protein kinase receptor FLT3	Homo sapiens	Inhibition	=	85.0	%	PMID[30742435]
NPT1650	Individual protein	Tyrosine-protein kinase receptor FLT3	Homo sapiens	Inhibition	=	52.0	%	PMID[30742435]
NPT1650	Individual protein	Tyrosine-protein kinase receptor FLT3	Homo sapiens	Inhibition	=	91.0	%	PMID[30742435]
NPT3364	Individual protein	Protein kinase C mu	Homo sapiens	IC50	=	500.0	nM	PMID[36538005]
NPT3364	Individual protein	Protein kinase C mu	Homo sapiens	Inhibition	=	94.0	%	PMID[36538005]
NPT28319	Chimeric protein	Nuclear receptor subfamily 2 group C member 2/TGF-beta-activated kinase 1 and MAP3K7-binding protein 1	Homo sapiens	IC50	=	30.0	nM	PMID[35834411]
NPT591	Individual protein	Glycogen synthase kinase-3 beta	Homo sapiens	IC50	=	11300.0	nM	PMID[33991821]
NPT591	Individual protein	Glycogen synthase kinase-3 beta	Homo sapiens	Inhibition	n.a.	n.a.	%	PMID[33991821]
NPT591	Individual protein	Glycogen synthase kinase-3 beta	Homo sapiens	IC50	=	663.0	nM	PMID[33991821]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT146	Cell line	SK-OV-3	Homo sapiens	IC50	=	70.0	nM	PMID[17067161]
NPT1915	Cell line	COLO-829	Homo sapiens	IC50	=	150.0	nM	PMID[17067161]
NPT139	Cell line	HT-29	Homo sapiens	IC50	=	5900.0	nM	PMID[17067161]
NPT83	Cell line	MCF7	Homo sapiens	IC50	=	16300.0	nM	PMID[21513293]
NPT397	Cell line	NCI-H460	Homo sapiens	IC50	=	4300.0	nM	PMID[21513293]
NPT395	Cell line	SF-268	Homo sapiens	IC50	=	12700.0	nM	PMID[21513293]
NPT165	Cell line	HeLa	Homo sapiens	IC50	=	1000.0	nM	PMID[28749671]
NPT81	Cell line	A549	Homo sapiens	IC50	=	1000.0	nM	PMID[28749671]
NPT83	Cell line	MCF7	Homo sapiens	IC50	=	3300.0	nM	PMID[28749671]
NPT1649	Cell line	MV4-11	Homo sapiens	IC50	=	15.0	nM	PMID[30742435]
NPT1970	Cell line	THP-1	Homo sapiens	IC50	>	1000.0	nM	PMID[30742435]
NPT15	Cell line	Jurkat	Homo sapiens	IC50	>	1000.0	nM	PMID[30742435]
NPT377	Cell line	OVCAR-3	Homo sapiens	IC50	=	2600.0	nM	PMID[35834411]
NPT400	Cell line	MDA-MB-435	Homo sapiens	IC50	=	1900.0	nM	PMID[35834411]
NPT25805	Organism	Phytophthora litchii	Phytophthora litchii	IC50	=	1900.0	nM	PMID[28749671]
NPT28438	Unchecked	Unchecked	n.a.	IC50	=	150.0	nM	PMID[30234295]
NPT1018	Organism	Trypanosoma brucei	Trypanosoma brucei	Activity	=	33.0	%	PMID[30234295]
NPT1018	Organism	Trypanosoma brucei	Trypanosoma brucei	EC50	=	170.0	nM	PMID[30234295]

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

Experimental ADME

Experiment Model	Experiment Tissue	ADME Type	ADME Relation	ADME Value	ADME Unit	Reference

Experimental Toxicity

Quantitative toxicity

Experiment Model	Experiment Organism	Toxicity Type	Toxicity Relation	Toxicity Value	Toxicity Unit	Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity	Carcinogenicity	Mutagenicity	Cardiotoxicity	Respiratory Toxicity	Eye Irritation	Endocrine Disruption

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]

Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

● The left chart: Distribution of similarity level between NPC99381 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	10364
0.1-0.2	36315
0.2-0.3	3064
0.3-0.4	73
0.4-0.5	25
0.5-0.6	7
0.6-0.7	6
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.7647	Intermediate Similarity	NPC469670
0.7647	Intermediate Similarity	NPC469619
0.7246	Intermediate Similarity	NPC606719
0.7059	Intermediate Similarity	NPC56204
0.662	Remote Similarity	NPC73411
0.662	Remote Similarity	NPC215711
0.662	Remote Similarity	NPC600572
0.662	Remote Similarity	NPC609200
0.662	Remote Similarity	NPC610004
0.6389	Remote Similarity	NPC602776
0.5921	Remote Similarity	NPC603296
0.5915	Remote Similarity	NPC107625
0.5811	Remote Similarity	NPC215921
0.5513	Remote Similarity	NPC603141
0.5513	Remote Similarity	NPC603437
0.5128	Remote Similarity	NPC86373
0.5128	Remote Similarity	NPC277426

Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

● The left chart: Distribution of similarity level between NPC99381 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3379
0.1-0.2	5687
0.2-0.3	83
0.3-0.4	1
0.4-0.5	0
0.5-0.6	0
0.6-0.7	0
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
		NPD

Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.
Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity

B: biological targets similarity

C: networks similarity

D: cell-based bioactivity similarity

E: similarity based on clinical data