NPASS Compound

Natural Product: NPC179059

Natural Product ID	NPC179059
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	VFKJAXDQCDDPCK-UHFFFAOYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	609122
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000145] Coumarins and derivatives

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 34 36 0 0 0 0 0 0 0 0999 V2000 -3.8787 -0.4684 1.0526 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5920 0.2261 -0.2393 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1969 1.5909 -0.4144 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2089 0.0803 -0.8746 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2099 -0.6521 -0.0912 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6795 -1.5844 0.6589 O 0 0 0 0 0 0 0 0 0 0 0 0 0.2149 -0.3819 -0.1259 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7360 0.6034 -0.9152 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1023 0.8593 -0.9456 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6153 1.8566 -1.7464 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9779 2.0513 -1.7238 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7629 1.2583 -0.9179 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0227 1.4890 -0.9413 O 0 0 0 0 0 0 0 0 0 0 0 0 4.2593 0.3178 -0.1654 O 0 0 0 0 0 0 0 0 0 0 0 0 2.9659 0.1086 -0.1655 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4475 -0.9003 0.6447 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0870 -1.1224 0.6464 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5271 -2.1192 1.4402 O 0 0 0 0 0 0 0 0 0 0 0 0 1.2637 -2.9582 2.2797 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3560 -0.5832 -1.3174 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.1432 -0.2107 1.8528 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9968 -1.5689 0.9485 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8881 -0.0926 1.3934 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6836 2.1758 -1.2251 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0229 2.1599 0.5222 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2667 1.5670 -0.6920 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8643 0.8814 -1.5332 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1069 1.2181 -1.5429 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9453 2.4313 -2.3449 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4195 2.8286 -2.3421 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1285 -1.4815 1.2504 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6099 -3.3782 3.0764 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6936 -3.8183 1.7343 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1014 -2.3839 2.7637 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 2 4 1 0 4 5 1 0 5 6 2 0 5 7 1 0 7 8 2 0 8 9 1 0 9 10 1 0 10 11 2 0 11 12 1 0 12 13 2 0 12 14 1 0 14 15 1 0 15 16 1 0 16 17 2 0 17 18 1 0 18 19 1 0 4 20 1 0 20 2 1 0 17 7 1 0 15 9 2 0 1 21 1 0 1 22 1 0 1 23 1 0 3 24 1 0 3 25 1 0 3 26 1 0 4 27 1 0 8 28 1 0 10 29 1 0 11 30 1 0 16 31 1 0 19 32 1 0 19 33 1 0 19 34 1 0 M END

Standard InCHIKey	VFKJAXDQCDDPCK-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C15H14O5/c1-15(2)14(20-15)13(17)9-6-8-4-5-12(16)19-10(8)7-11(9)18-3/h4-7,14H,1-3H3
SMILES	CC1(C)C(C(=O)c2cc3ccc(=O)oc3cc2OC)O1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	274.08	Volume:	270.459 ? Van der Waals volume.
Dense:	1.013	LogP:	2.062 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.255 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.028 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	16.0
TPSA:	69.04 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	0.0	Rings:	3.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.487	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.998	Fsp³:	0.333
MCE-18:	60.8 ? 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:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.091	Fluc inhibitor:	0.064 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.994 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.38 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.448	Promiscuous compounds:	0.107

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.505	MDCK Permeability:	-4.572
Pgp-inhibitor:	0.024	Pgp-substrate:	0.0
PAMPA:	0.373 ? 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):	0.001
20% Bioavailability (F20%):	0.383	30% Bioavailability (F30%):	0.221
50% Bioavailability (F50%):	0.302

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.002	MRP1:	0.999
Plasma Protein Binding (PPB):	80.259%	Volume Distribution (VD):	0.043
Fu:	19.887% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.987
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.0
BSEP inhibitor:	0.998

ADMET: Metabolism

CYP1A2-inhibitor:	0.012	CYP1A2-substrate:	0.071
CYP2C19-inhibitor:	0.973	CYP2C19-substrate:	0.013
CYP2C9-inhibitor:	0.364	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.006	CYP2D6-substrate:	0.408
CYP3A4-inhibitor:	0.163	CYP3A4-substrate:	0.055
CYP2B6-substrate:	0.317	CYP2C8-inhibitor:	0.181
HLM stability:	0.239 ? 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):

6.042

Half-life (T1/2):

0.851

ADMET: Toxicity

hERG Blockers:	0.123	hERG Blockers (10um):	0.359
Human Hepatotoxicity (H-HT):	0.485	Drug-induced Liver Injury (DILI):	0.755
AMES Toxicity:	0.701	Rat Oral Acute Toxicity:	0.563
Maximum Recommended Daily Dose:	0.644	Skin Sensitization:	0.471
Carcinogencity:	0.778	Eye Corrosion:	0.16
Eye Irritation:	0.952	Respiratory Toxicity:	0.63
Drug-induced Neurotoxicity:	0.5	Ototoxicity:	0.179
Hematotoxicity:	0.341	Drug-induced Nephrotoxicity:	0.228
Genotoxicity:	0.911	RPMI-8226 Immunitoxicity:	0.095
A549 Cytotoxicity:	0.046	Hek293 Cytotoxicity:	0.297
BCF:	1.145 ? 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:	3.751 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.504 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.901 ? 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
NPO18265	Citrus tamurana	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[11999424]
NPO15730.1	Citrus medica var. etrog	Varieties	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO18265	Citrus tamurana	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO12100	Citrus sulcata	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO18265	Citrus tamurana	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO12100	Citrus sulcata	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO15730.1	Citrus medica var. etrog	Varieties	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO12100	Citrus sulcata	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO18265	Citrus tamurana	Species	Rutaceae	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

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

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 NPC179059 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	24690
0.1-0.2	23003
0.2-0.3	1795
0.3-0.4	273
0.4-0.5	73
0.5-0.6	23
0.6-0.7	1
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
0.7708	Intermediate Similarity	NPC605579
0.6852	Remote Similarity	NPC36414
0.5902	Remote Similarity	NPC76657
0.569	Remote Similarity	NPC72281
0.5593	Remote Similarity	NPC601133
0.5593	Remote Similarity	NPC608534
0.5517	Remote Similarity	NPC248429
0.55	Remote Similarity	NPC204353
0.5345	Remote Similarity	NPC80170
0.5294	Remote Similarity	NPC151946
0.5254	Remote Similarity	NPC111347
0.5246	Remote Similarity	NPC76753
0.5192	Remote Similarity	NPC265547
0.5192	Remote Similarity	NPC240722
0.5167	Remote Similarity	NPC253574
0.5167	Remote Similarity	NPC257188
0.5167	Remote Similarity	NPC234109
0.5167	Remote Similarity	NPC98179
0.5167	Remote Similarity	NPC188327
0.5147	Remote Similarity	NPC7526
0.5147	Remote Similarity	NPC222036
0.5147	Remote Similarity	NPC14248
0.5082	Remote Similarity	NPC78746
0.5075	Remote Similarity	NPC119640
0.5075	Remote Similarity	NPC183646

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC179059 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3769
0.1-0.2	5227
0.2-0.3	146
0.3-0.4	8
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