NPASS Compound

Natural Product: NPC603790

Natural Product ID	NPC603790
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	KBHLNNQHHPFDSG-VTGIHGMASA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL2059294
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds]

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 56 56 0 0 0 0 0 0 0 0999 V2000 -7.6538 -0.0465 -1.2281 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.3070 -1.0614 -2.2859 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3395 -2.0894 -1.8450 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9816 -1.6811 -1.4520 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8208 -0.7321 -0.3229 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3262 -0.4695 -0.0377 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2013 0.4981 1.1143 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7543 0.7949 1.4414 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9850 -0.4196 1.8250 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4367 -0.0376 2.1421 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1719 0.6016 0.9921 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5748 0.9067 1.4838 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4025 1.5608 0.3817 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7454 1.8199 0.9491 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8558 1.3273 0.4853 C 0 0 0 0 0 0 0 0 0 0 0 0 7.2197 1.5220 0.9713 C 0 0 0 0 0 0 0 0 0 0 0 0 7.5514 2.2563 1.9404 O 0 0 0 0 0 0 0 0 0 0 0 0 8.0782 0.7466 0.1649 O 0 0 0 0 0 0 0 0 0 0 0 0 7.2673 -0.3194 -0.3037 C 0 0 2 0 0 0 0 0 0 0 0 0 7.8480 -1.0435 -1.4662 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9831 0.4365 -0.6689 C 0 0 2 0 0 0 0 0 0 0 0 0 6.3186 1.2336 -1.7791 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.2499 0.9353 -1.5224 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4394 -0.3648 -0.2020 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.7840 0.1253 -1.2239 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.2808 -1.5216 -2.6389 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9498 -0.5323 -3.2277 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2258 -2.8132 -2.7186 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8512 -2.7268 -1.0721 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3983 -2.6354 -1.2563 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4447 -1.2430 -2.3513 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2528 -1.1378 0.6036 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2355 0.2753 -0.5673 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8985 -0.0129 -0.9492 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8358 -1.4229 0.1370 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7345 0.0694 1.9851 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6940 1.4585 0.8658 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7477 1.4915 2.3047 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2693 1.3184 0.5925 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4011 -0.8494 2.7739 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9384 -1.1892 1.0246 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0088 -0.9045 2.5451 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3839 0.7334 2.9482 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1973 -0.1128 0.1593 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7140 1.5792 0.7374 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5171 1.5432 2.3900 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0139 -0.0596 1.8072 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8640 2.5108 0.1267 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3956 0.8950 -0.4744 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7965 2.4686 1.8138 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9751 -0.9986 0.5445 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3497 -0.8164 -2.4304 H 0 0 0 0 0 0 0 0 0 0 0 0 8.9481 -0.9146 -1.5221 H 0 0 0 0 0 0 0 0 0 0 0 0 7.6977 -2.1465 -1.2783 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1440 -0.2256 -0.8509 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5418 1.4199 -2.3529 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 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 11 12 1 0 12 13 1 0 13 14 1 0 14 15 2 0 15 16 1 0 16 17 2 0 16 18 1 0 18 19 1 0 19 20 1 0 19 21 1 0 21 22 1 0 21 15 1 0 1 23 1 0 1 24 1 0 1 25 1 0 2 26 1 0 2 27 1 0 3 28 1 0 3 29 1 0 4 30 1 0 4 31 1 0 5 32 1 0 5 33 1 0 6 34 1 0 6 35 1 0 7 36 1 0 7 37 1 0 8 38 1 0 8 39 1 0 9 40 1 0 9 41 1 0 10 42 1 0 10 43 1 0 11 44 1 0 11 45 1 0 12 46 1 0 12 47 1 0 13 48 1 0 13 49 1 0 14 50 1 0 19 51 1 1 20 52 1 0 20 53 1 0 20 54 1 0 21 55 1 6 22 56 1 0 M END

Standard InCHIKey	KBHLNNQHHPFDSG-VTGIHGMASA-N
Standard InCHI	InChI=1S/C19H34O3/c1-3-4-5-6-7-8-9-10-11-12-13-14-15-17-18(20)16(2)22-19(17)21/h15-16,18,20H,3-14H2,1-2H3/b17-15+/t16-,18+/m1/s1
SMILES	CCCCCCCCCCCCC/C=C1/C(=O)O[C@H](C)[C@@H]1O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	310.25	Volume:	349.721 ? Van der Waals volume.
Dense:	0.887	LogP:	5.94 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.198 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.182 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	12.0	Rigid Bonds:	7.0
TPSA:	46.53 ? Topological Polar Surface Area.	H-Bond Acceptor:	3.0
H-Bond Donor:	1.0	Rings:	1.0
Heavy Atoms:	3.0

MedChem Properties

QED Drug-Likeness Score:	0.316	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.27	Fsp³:	0.842
MCE-18:	14.8 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted	GSK Rule:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.613	Fluc inhibitor:	0.103 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.044 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.018 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.933	Promiscuous compounds:	0.206

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.031	MDCK Permeability:	-4.731
Pgp-inhibitor:	0.026	Pgp-substrate:	0.024
PAMPA:	0.003 ? The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).	Human Intestinal Absorption (HIA):	0.899
20% Bioavailability (F20%):	0.971	30% Bioavailability (F30%):	0.996
50% Bioavailability (F50%):	0.949

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.007	MRP1:	0.646
Plasma Protein Binding (PPB):	99.342%	Volume Distribution (VD):	1.119
Fu:	0.896% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.845
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.402
BSEP inhibitor:	0.806

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.918
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.089
CYP2C9-inhibitor:	0.075	CYP2C9-substrate:	0.078
CYP2D6-inhibitor:	0.204	CYP2D6-substrate:	0.117
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.04 ? Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):

4.193

Half-life (T1/2):

0.807

ADMET: Toxicity

hERG Blockers:	0.223	hERG Blockers (10um):	0.717
Human Hepatotoxicity (H-HT):	0.728	Drug-induced Liver Injury (DILI):	0.549
AMES Toxicity:	0.595	Rat Oral Acute Toxicity:	0.554
Maximum Recommended Daily Dose:	0.762	Skin Sensitization:	1.0
Carcinogencity:	0.619	Eye Corrosion:	0.075
Eye Irritation:	0.902	Respiratory Toxicity:	0.864
Drug-induced Neurotoxicity:	0.2	Ototoxicity:	0.332
Hematotoxicity:	0.629	Drug-induced Nephrotoxicity:	0.875
Genotoxicity:	0.004	RPMI-8226 Immunitoxicity:	0.195
A549 Cytotoxicity:	0.982	Hek293 Cytotoxicity:	0.504
BCF:	1.016 ? Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].	IGC50:	4.662 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.104 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.38 ? 96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO61198	Mollinedia marliae	Genus	Monimiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]

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
Activity	2
Inhibition	7

Activity Type	# Activity
Cell line	3
Individual protein	2
Single protein	1
Unchecked	3

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT861	Individual protein	Isocitrate dehydrogenase [NADP] cytoplasmic	Homo sapiens	Activity	=	110.8	%	PMID[26508549]
NPT861	Individual protein	Isocitrate dehydrogenase [NADP] cytoplasmic	Homo sapiens	Activity	=	113.7	%	PMID[26508549]
NPT29646	Single protein	14-3-3 protein epsilon	Homo sapiens	Inhibition	n.a.	n.a.	%	PMID[25205188]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT139	Cell line	HT-29	Homo sapiens	Inhibition	n.a.	n.a.	%	PMID[25205188]
NPT28438	Unchecked	Unchecked	n.a.	Inhibition	n.a.	n.a.	%	PMID[22578462]

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 NPC603790 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	11721
0.1-0.2	31106
0.2-0.3	6362
0.3-0.4	602
0.4-0.5	40
0.5-0.6	9
0.6-0.7	11
0.7-0.8	0
0.8-0.85	2
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC47148
0.8485	Intermediate Similarity	NPC605151
0.8	Intermediate Similarity	NPC150502
0.7568	Intermediate Similarity	NPC604911
0.6053	Remote Similarity	NPC125365
0.6053	Remote Similarity	NPC256640
0.6053	Remote Similarity	NPC51809
0.6053	Remote Similarity	NPC301207
0.6053	Remote Similarity	NPC221095
0.6053	Remote Similarity	NPC279214
0.6053	Remote Similarity	NPC16279
0.6053	Remote Similarity	NPC474818
0.6053	Remote Similarity	NPC49302
0.6053	Remote Similarity	NPC176329
0.6053	Remote Similarity	NPC205615
0.575	Remote Similarity	NPC229799
0.575	Remote Similarity	NPC284472
0.575	Remote Similarity	NPC474959
0.575	Remote Similarity	NPC310450
0.575	Remote Similarity	NPC286770
0.575	Remote Similarity	NPC11383
0.5641	Remote Similarity	NPC608765
0.5641	Remote Similarity	NPC609320
0.561	Remote Similarity	NPC473471

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC603790 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5428
0.1-0.2	3517
0.2-0.3	196
0.3-0.4	9
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