NPASS Compound

Natural Product: NPC488731

Natural Product ID	NPC488731
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	KIIBBMRZUILYPB-XURGJTJWSA-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 66 68 0 0 0 0 0 0 0 0999 V2000 7.0700 0.3756 2.8644 C 0 0 0 0 0 0 0 0 0 0 0 0 7.6238 -0.1426 1.5978 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0549 0.1026 0.4387 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8268 0.9083 0.3043 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6980 0.0971 -0.3360 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4710 0.9333 -0.4609 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9071 1.1904 -1.6323 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6927 2.0275 -1.6739 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5087 1.3637 -2.2725 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0408 0.1319 -1.5901 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2065 0.0703 -1.0523 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7414 -1.1177 -0.3600 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0046 -1.6387 -0.8669 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1985 -1.0547 -0.5065 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4166 -1.5021 -1.0042 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4727 -2.5479 -1.8769 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2972 -3.1543 -2.2559 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0945 -2.7074 -1.7602 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9212 -3.3241 -2.1464 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.3843 -4.2175 -3.1451 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.5584 -0.9310 -0.6467 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.6254 0.0776 0.1882 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.8451 0.6483 0.5368 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.9038 1.7200 1.4252 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.7620 2.2406 1.9794 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5638 1.6578 1.6186 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4792 0.6036 0.7474 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2746 0.0030 0.3709 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2396 0.4580 0.8636 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.4033 2.1744 2.1715 O 0 0 0 0 0 0 0 0 0 0 0 0 -9.1344 2.2901 1.7721 O 0 0 0 0 0 0 0 0 0 0 0 0 0.8638 -1.0997 -1.4581 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8456 1.5053 0.7587 C 0 0 0 0 0 0 0 0 0 0 0 0 8.8713 -0.9706 1.6552 C 0 0 0 0 0 0 0 0 0 0 0 0 6.1344 -0.2191 3.0702 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8253 1.4461 2.7860 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7821 0.2364 3.6999 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4864 -0.2931 -0.4800 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4868 1.3548 1.2514 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0033 1.7603 -0.3946 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4589 -0.7917 0.2685 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0124 -0.2411 -1.3328 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3498 0.7828 -2.5302 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9497 2.8925 -2.3596 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4845 2.5106 -0.6933 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7940 1.0253 -3.3153 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3350 2.0734 -2.4585 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7455 1.0123 -1.2179 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9874 -1.9428 -0.6136 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6107 -1.1170 0.7388 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4442 -2.8759 -2.2509 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9159 -4.2857 -2.4895 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9109 -5.0888 -2.9401 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.7558 0.2566 0.1142 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8573 3.0701 2.6619 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4349 2.4521 3.1444 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.6696 2.7132 1.0205 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8882 -0.9961 -1.8779 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4102 -1.9447 -2.0597 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9671 -1.4162 -0.4015 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3505 1.1006 1.6603 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9635 2.6201 0.7832 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7776 1.2219 0.8589 H 0 0 0 0 0 0 0 0 0 0 0 0 8.6386 -2.0582 1.7458 H 0 0 0 0 0 0 0 0 0 0 0 0 9.4109 -0.7854 0.6847 H 0 0 0 0 0 0 0 0 0 0 0 0 9.5454 -0.6444 2.4768 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 1 0 6 7 2 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 2 0 11 12 1 0 12 13 1 0 13 14 2 0 14 15 1 0 15 16 2 0 16 17 1 0 17 18 2 0 18 19 1 0 17 20 1 0 15 21 1 0 21 22 1 0 22 23 2 0 23 24 1 0 24 25 2 0 25 26 1 0 26 27 2 0 27 28 1 0 28 29 2 0 26 30 1 0 24 31 1 0 10 32 1 0 6 33 1 0 2 34 1 0 18 13 1 0 27 22 1 0 28 14 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 5 41 1 0 5 42 1 0 7 43 1 0 8 44 1 0 8 45 1 0 9 46 1 0 9 47 1 0 11 48 1 0 12 49 1 0 12 50 1 0 16 51 1 0 19 52 1 0 20 53 1 0 23 54 1 0 25 55 1 0 30 56 1 0 31 57 1 0 32 58 1 0 32 59 1 0 32 60 1 0 33 61 1 0 33 62 1 0 33 63 1 0 34 64 1 0 34 65 1 0 34 66 1 0 M END

Standard InCHIKey	KIIBBMRZUILYPB-XURGJTJWSA-N
Standard InCHI	InChI=1S/C28H32O6/c1-16(2)7-5-8-17(3)9-6-10-18(4)11-12-20-25-24(15-22(31)27(20)32)34-23-14-19(29)13-21(30)26(23)28(25)33/h7,9,11,13-15,29-32H,5-6,8,10,12H2,1-4H3/b17-9+,18-11+
SMILES	CC(=CCC/C(=C/CC/C(=C/Cc1c2c(cc(c1O)O)oc1cc(cc(c1c2=O)O)O)/C)/C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	464.22	Volume:	493.551 ? Van der Waals volume.
Dense:	0.941	LogP:	7.546 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.704 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.283 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	8.0	Rigid Bonds:	20.0
TPSA:	111.13 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	4.0	Rings:	3.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.167	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.259	Fsp³:	0.321
MCE-18:	22.0 ? 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:	1
Colloidal aggregators:	0.997	Fluc inhibitor:	0.455 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.933 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.645 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.416	Promiscuous compounds:	0.087

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.189	MDCK Permeability:	-4.86
Pgp-inhibitor:	0.99	Pgp-substrate:	0.042
PAMPA:	0.007 ? 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):	0.003
20% Bioavailability (F20%):	0.071	30% Bioavailability (F30%):	0.649
50% Bioavailability (F50%):	0.992

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.966
Plasma Protein Binding (PPB):	97.575%	Volume Distribution (VD):	0.089
Fu:	2.235% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.996	BCRP inhibitor:	0.217
BSEP inhibitor:	0.996

ADMET: Metabolism

CYP1A2-inhibitor:	0.007	CYP1A2-substrate:	0.936
CYP2C19-inhibitor:	0.345	CYP2C19-substrate:	0.919
CYP2C9-inhibitor:	0.875	CYP2C9-substrate:	0.45
CYP2D6-inhibitor:	1.0	CYP2D6-substrate:	1.0
CYP3A4-inhibitor:	0.005	CYP3A4-substrate:	0.992
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):

5.276

Half-life (T1/2):

1.331

ADMET: Toxicity

hERG Blockers:	0.087	hERG Blockers (10um):	0.679
Human Hepatotoxicity (H-HT):	0.759	Drug-induced Liver Injury (DILI):	0.843
AMES Toxicity:	0.16	Rat Oral Acute Toxicity:	0.564
Maximum Recommended Daily Dose:	0.83	Skin Sensitization:	0.974
Carcinogencity:	0.317	Eye Corrosion:	0.0
Eye Irritation:	0.941	Respiratory Toxicity:	0.974
Drug-induced Neurotoxicity:	0.034	Ototoxicity:	0.31
Hematotoxicity:	0.094	Drug-induced Nephrotoxicity:	0.07
Genotoxicity:	0.99	RPMI-8226 Immunitoxicity:	0.053
A549 Cytotoxicity:	0.684	Hek293 Cytotoxicity:	0.741
BCF:	2.086 ? 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:	5.619 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	7.17 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	7.028 ? 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
NPO25472	Garcinia cowa	Species	Clusiaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1071/CH03175]
NPO25472	Garcinia cowa	Species	Clusiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19299148]
NPO25472	Garcinia cowa	Species	Clusiaceae	Eukaryota	twigs	n.a.	n.a.	PMID[20058933]
NPO25472	Garcinia cowa	Species	Clusiaceae	Eukaryota	young fruits	Khokkhon, Tha Bo District, Nong Khai Province, Thailand	2011-Aug	PMID[25651042]
NPO25472	Garcinia cowa	Species	Clusiaceae	Eukaryota	flowers	Pakook, Muang District, Chiang Rai Province, Thailand	2013-Feb	PMID[25651042]
NPO25472	Garcinia cowa	Species	Clusiaceae	Eukaryota	Leaves	n.a.	n.a.	PMID[31860303]
NPO25472	Garcinia cowa	Species	Clusiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO25472	Garcinia cowa	Species	Clusiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO25472	Garcinia cowa	Species	Clusiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO25472	Garcinia cowa	Species	Clusiaceae	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	1

Activity Type	# Activity
Protein family	1

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
NPT20648	Protein family	Alpha glucosidase	Homo sapiens	IC50	=	76200.0	nM	PMID[31860303]

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 NPC488731 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	22297
0.1-0.2	24721
0.2-0.3	2381
0.3-0.4	374
0.4-0.5	59
0.5-0.6	17
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
0.7869	Intermediate Similarity	NPC89474
0.7606	Intermediate Similarity	NPC488730
0.7606	Intermediate Similarity	NPC488729
0.7143	Intermediate Similarity	NPC236796
0.6944	Remote Similarity	NPC300727
0.6087	Remote Similarity	NPC329091
0.5714	Remote Similarity	NPC142339
0.5696	Remote Similarity	NPC476242
0.5625	Remote Similarity	NPC202157
0.5616	Remote Similarity	NPC235018
0.5493	Remote Similarity	NPC274730
0.5488	Remote Similarity	NPC80534
0.5479	Remote Similarity	NPC241904
0.5405	Remote Similarity	NPC45146
0.5316	Remote Similarity	NPC320359
0.525	Remote Similarity	NPC13408
0.5181	Remote Similarity	NPC206153
0.5181	Remote Similarity	NPC271629
0.5132	Remote Similarity	NPC604618
0.5122	Remote Similarity	NPC40491
0.5122	Remote Similarity	NPC479164
0.5122	Remote Similarity	NPC278052
0.5057	Remote Similarity	NPC479158

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC488731 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4837
0.1-0.2	4279
0.2-0.3	30
0.3-0.4	4
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