NPASS Compound

Natural Product: NPC479157

Natural Product ID	NPC479157
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	HXNGHHMZQLUJNN-UHFFFAOYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
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 64 67 0 0 0 0 0 0 0 0999 V2000 5.4523 -2.7159 0.8420 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4968 -1.9503 -0.4142 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2980 -0.6674 -0.4801 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9984 0.1903 0.6834 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0172 1.2522 0.4519 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6613 1.1165 0.4425 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7829 2.1735 0.1750 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2963 3.4069 -0.0910 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6565 3.6092 -0.0955 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4633 2.5604 0.1680 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8468 2.7944 0.1578 O 0 0 0 0 0 0 0 0 0 0 0 0 6.5885 2.6405 -1.0575 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1969 4.8823 -0.3690 O 0 0 0 0 0 0 0 0 0 0 0 0 0.4728 1.9768 0.1830 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0898 0.8210 0.4342 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4572 0.6457 0.4362 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3451 1.7672 0.1505 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6617 1.6596 0.1382 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3157 0.3644 0.4207 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1880 0.5391 1.6583 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2018 -0.0044 -0.7788 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8784 -1.2994 -0.5423 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.1839 -1.4660 -0.5110 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.1331 -0.3471 -0.7143 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.7447 -2.8359 -0.2609 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4492 -0.6963 0.6914 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.0733 -0.5602 0.6986 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2367 -1.6450 0.9735 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1303 -1.4840 0.9745 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7137 -0.2629 0.7078 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0789 -0.0818 0.7042 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7792 -1.0584 0.9522 O 0 0 0 0 0 0 0 0 0 0 0 0 0.9900 -2.5482 1.2452 O 0 0 0 0 0 0 0 0 0 0 0 0 5.7918 -2.6682 -1.7220 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2056 -3.5687 0.7834 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4550 -3.1538 1.0546 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7807 -2.0762 1.6791 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3518 -0.1530 -1.4748 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8479 -0.3513 1.6401 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9878 0.7061 0.8892 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6211 4.2264 -0.2994 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3176 1.8247 -0.9054 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9022 2.3253 -1.8743 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1200 3.5813 -1.3151 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9789 5.2906 -1.2782 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8584 2.7203 -0.0571 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2700 2.5556 -0.0874 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4859 1.5940 1.7933 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1322 -0.0385 1.5683 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6802 0.1810 2.5783 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9640 0.7807 -0.9537 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5283 -0.0581 -1.6668 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2384 -2.1580 -0.3861 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.1697 -0.6636 -0.4617 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.8137 0.4918 -0.0583 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.1681 -0.0371 -1.7860 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4313 -3.5327 -1.0742 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.8428 -2.8348 -0.1982 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3444 -3.2521 0.6867 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6978 -2.6121 1.1851 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6535 -3.4204 1.6437 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8505 -2.4267 -1.9741 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7186 -3.7565 -1.5383 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0807 -2.2932 -2.4695 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 3 3 4 1 0 4 5 1 0 5 6 2 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 2 0 10 11 1 0 11 12 1 0 9 13 1 0 7 14 1 0 14 15 1 0 15 16 2 0 16 17 1 0 17 18 2 0 18 19 1 0 19 20 1 0 19 21 1 0 21 22 1 0 22 23 2 3 23 24 1 0 23 25 1 0 19 26 1 0 26 27 1 0 27 28 2 0 28 29 1 0 29 30 2 0 30 31 1 0 31 32 2 0 29 33 1 0 2 34 1 0 10 5 1 0 30 15 1 0 31 6 1 0 27 16 1 0 1 35 1 0 1 36 1 0 1 37 1 0 3 38 1 0 4 39 1 0 4 40 1 0 8 41 1 0 12 42 1 0 12 43 1 0 12 44 1 0 13 45 1 0 17 46 1 0 18 47 1 0 20 48 1 0 20 49 1 0 20 50 1 0 21 51 1 0 21 52 1 0 22 53 1 0 24 54 1 0 24 55 1 0 24 56 1 0 25 57 1 0 25 58 1 0 25 59 1 0 28 60 1 0 33 61 1 0 34 62 1 0 34 63 1 0 34 64 1 0 M END

Standard InCHIKey	HXNGHHMZQLUJNN-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C28H30O6/c1-15(2)7-8-18-23-22(14-20(30)26(18)32-6)33-27-17-10-12-28(5,11-9-16(3)4)34-21(17)13-19(29)24(27)25(23)31/h7,9-10,12-14,29-30H,8,11H2,1-6H3
SMILES	CC(=CCc1c2c(cc(c1OC)O)oc1c3C=CC(C)(CC=C(C)C)Oc3cc(c1c2=O)O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	462.2	Volume:	484.995 ? Van der Waals volume.
Dense:	0.953	LogP:	6.727 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.535 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.473 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	24.0
TPSA:	89.13 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	2.0	Rings:	4.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.337	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.987	Fsp³:	0.321
MCE-18:	85.514 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.995	Fluc inhibitor:	0.496 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.871 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.947 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.205	Promiscuous compounds:	0.187

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.849	MDCK Permeability:	-4.61
Pgp-inhibitor:	0.993	Pgp-substrate:	0.373
PAMPA:	0.046 ? 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):	0.01
20% Bioavailability (F20%):	0.913	30% Bioavailability (F30%):	0.993
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.005	MRP1:	0.967
Plasma Protein Binding (PPB):	95.856%	Volume Distribution (VD):	0.2
Fu:	3.873% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.934	BCRP inhibitor:	0.972
BSEP inhibitor:	0.997

ADMET: Metabolism

CYP1A2-inhibitor:	0.001	CYP1A2-substrate:	1.0
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.997
CYP2C9-inhibitor:	0.035	CYP2C9-substrate:	0.585
CYP2D6-inhibitor:	0.928	CYP2D6-substrate:	0.253
CYP3A4-inhibitor:	0.304	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	1.0 ? 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):

3.003

Half-life (T1/2):

1.328

ADMET: Toxicity

hERG Blockers:	0.038	hERG Blockers (10um):	0.5
Human Hepatotoxicity (H-HT):	0.557	Drug-induced Liver Injury (DILI):	0.905
AMES Toxicity:	0.659	Rat Oral Acute Toxicity:	0.892
Maximum Recommended Daily Dose:	0.499	Skin Sensitization:	0.903
Carcinogencity:	0.71	Eye Corrosion:	0.0
Eye Irritation:	0.262	Respiratory Toxicity:	0.931
Drug-induced Neurotoxicity:	0.134	Ototoxicity:	0.42
Hematotoxicity:	0.205	Drug-induced Nephrotoxicity:	0.482
Genotoxicity:	0.91	RPMI-8226 Immunitoxicity:	0.047
A549 Cytotoxicity:	0.321	Hek293 Cytotoxicity:	0.459
BCF:	2.24 ? 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:	5.101 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	7.183 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	6.54 ? 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
NPO40853	Garcinia tetrandra	Species	Clusiaceae	Eukaryota	Stem Bark	n.a.	n.a.	PMID[30978023]
NPO40853	Garcinia tetrandra	Species	Clusiaceae	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
IC50	5

Activity Type	# Activity
Cell line	5

Molecular-level activity

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

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT83	Cell line	MCF7	Homo sapiens	IC50	>	10000.0	nM	PMID[30978023]
NPT91	Cell line	KB	Homo sapiens	IC50	>	10000.0	nM	PMID[30978023]
NPT65	Cell line	HepG2	Homo sapiens	IC50	>	10000.0	nM	PMID[30978023]
NPT139	Cell line	HT-29	Homo sapiens	IC50	>	10000.0	nM	PMID[30978023]
NPT20987	Cell line	HeLa S3	Homo sapiens	IC50	>	10000.0	nM	PMID[30978023]

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 NPC479157 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	16465
0.1-0.2	29191
0.2-0.3	3797
0.3-0.4	317
0.4-0.5	56
0.5-0.6	27
0.6-0.7	2
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
0.7848	Intermediate Similarity	NPC479156
0.6076	Remote Similarity	NPC220313
0.6026	Remote Similarity	NPC479160
0.5976	Remote Similarity	NPC275780
0.5714	Remote Similarity	NPC95842
0.5698	Remote Similarity	NPC206153
0.5698	Remote Similarity	NPC271629
0.5641	Remote Similarity	NPC241904
0.5595	Remote Similarity	NPC236521
0.557	Remote Similarity	NPC14353
0.5556	Remote Similarity	NPC39091
0.5529	Remote Similarity	NPC482612
0.5375	Remote Similarity	NPC228785
0.5349	Remote Similarity	NPC117854
0.5294	Remote Similarity	NPC248638
0.5281	Remote Similarity	NPC479155
0.5233	Remote Similarity	NPC300727
0.5227	Remote Similarity	NPC482611
0.5176	Remote Similarity	NPC32694
0.5169	Remote Similarity	NPC481610
0.5119	Remote Similarity	NPC478517
0.5116	Remote Similarity	NPC38219
0.5116	Remote Similarity	NPC310349
0.5114	Remote Similarity	NPC239752
0.5114	Remote Similarity	NPC40491
0.5114	Remote Similarity	NPC278052
0.5111	Remote Similarity	NPC481611
0.506	Remote Similarity	NPC55662
0.5057	Remote Similarity	NPC152659
0.5056	Remote Similarity	NPC472402

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC479157 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3548
0.1-0.2	5560
0.2-0.3	40
0.3-0.4	2
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