NPASS Compound

Natural Product: NPC488504

Natural Product ID	NPC488504
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	YGILXMANNHJYJZ-QDNVUCNISA-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] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001551] Diterpenoids

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 55 56 0 0 0 0 0 0 0 0999 V2000 3.9351 1.6258 -1.0859 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8581 0.4544 -0.1758 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9662 -0.1376 0.1803 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2976 0.2685 -0.2535 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5023 1.2441 -1.0242 O 0 0 0 0 0 0 0 0 0 0 0 0 7.4303 -0.4110 0.1677 O 0 0 0 0 0 0 0 0 0 0 0 0 2.5071 -0.0182 0.3110 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6731 -0.3974 -0.8248 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3036 -0.8970 -0.5857 C 0 0 1 0 0 0 0 0 0 0 0 0 0.2061 -2.1128 0.2299 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2378 -2.9220 0.3687 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0418 -2.4863 0.9182 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2519 -1.7328 0.5821 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0521 -0.5314 -0.3001 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2039 0.3842 -0.2963 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.3979 -0.4159 -0.8474 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9867 1.5075 -1.2678 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7582 2.2567 -0.8110 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5314 1.3953 -0.7887 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6879 0.0943 -0.0666 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.5009 0.2275 1.4265 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6431 0.9404 1.0085 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7550 1.7786 0.7324 O 0 0 0 0 0 0 0 0 0 0 0 0 4.5399 2.4421 -0.6404 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4201 1.3690 -2.0647 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9259 2.0655 -1.2486 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8990 -0.9940 0.8466 H 0 0 0 0 0 0 0 0 0 0 0 0 8.3144 -0.3930 -0.3258 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0975 0.9083 0.8180 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6954 -0.7204 1.1089 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1915 -1.1518 -1.4537 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5954 0.4968 -1.5113 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0782 -1.1997 -1.6128 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1788 -3.8188 0.9659 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1644 -2.6809 -0.1318 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1669 -3.5961 0.7177 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8526 -2.4507 2.0122 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8315 -1.4352 1.4913 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9604 -2.4175 0.0297 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9873 -0.9447 -1.3552 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0630 -1.1489 -1.6080 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1360 0.2432 -1.3265 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8690 -1.0060 -0.0165 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8527 2.1950 -1.1810 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8980 1.1979 -2.3086 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9461 2.8079 0.1322 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5767 3.0516 -1.5834 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2651 1.2081 -1.8549 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2757 1.9752 -0.3020 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3517 -0.3943 1.8074 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3723 -0.1172 2.0185 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3636 1.2977 1.6887 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0326 0.1908 1.7213 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9097 1.6334 1.4869 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5945 1.2720 0.7497 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 3 4 1 0 4 5 2 0 4 6 1 0 2 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 2 0 10 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 6 15 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 1 1 15 22 1 0 22 23 1 0 20 9 1 0 20 14 1 0 1 24 1 0 1 25 1 0 1 26 1 0 3 27 1 0 6 28 1 0 7 29 1 0 7 30 1 0 8 31 1 0 8 32 1 0 9 33 1 6 11 34 1 0 11 35 1 0 12 36 1 0 12 37 1 0 13 38 1 0 13 39 1 0 14 40 1 0 16 41 1 0 16 42 1 0 16 43 1 0 17 44 1 0 17 45 1 0 18 46 1 0 18 47 1 0 19 48 1 0 19 49 1 0 21 50 1 0 21 51 1 0 21 52 1 0 22 53 1 0 22 54 1 0 23 55 1 0 M END

Standard InCHIKey	YGILXMANNHJYJZ-QDNVUCNISA-N
Standard InCHI	InChI=1S/C20H32O3/c1-14(12-18(22)23)6-8-16-15(2)7-9-17-19(3,13-21)10-5-11-20(16,17)4/h12,16-17,21H,2,5-11,13H2,1,3-4H3,(H,22,23)/b14-12+/t16-,17?,19+,20+/m0/s1
SMILES	C/C(=CC(=O)O)/CC[C@H]1C(=C)CCC2[C@](C)(CCC[C@]12C)CO

Calculated Properties

Physi-Chem Properties

Molecular Weight:	320.24	Volume:	355.825 ? Van der Waals volume.
Dense:	0.9	LogP:	3.421 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.833 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.948 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	14.0
TPSA:	57.53 ? Topological Polar Surface Area.	H-Bond Acceptor:	3.0
H-Bond Donor:	2.0	Rings:	2.0
Heavy Atoms:	3.0

MedChem Properties

QED Drug-Likeness Score:	0.576	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.186	Fsp³:	0.75
MCE-18:	42.743 ? 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:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.032	Fluc inhibitor:	0.001 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.003 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.009 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.775	Promiscuous compounds:	0.371

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.73	MDCK Permeability:	-4.837
Pgp-inhibitor:	0.0	Pgp-substrate:	0.0
PAMPA:	0.888 ? 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%):	0.025	30% Bioavailability (F30%):	0.005
50% Bioavailability (F50%):	0.454

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.009	MRP1:	0.852
Plasma Protein Binding (PPB):	75.942%	Volume Distribution (VD):	-0.575
Fu:	21.609% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.996
OATP1B3 inhibitor:	0.978	BCRP inhibitor:	0.004
BSEP inhibitor:	0.263

ADMET: Metabolism

CYP1A2-inhibitor:	0.048	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.995	CYP2C19-substrate:	0.001
CYP2C9-inhibitor:	0.943	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.028	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.158	CYP3A4-substrate:	0.035
CYP2B6-substrate:	0.024	CYP2C8-inhibitor:	0.159
HLM stability:	0.012 ? 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):

4.4

Half-life (T1/2):

0.76

ADMET: Toxicity

hERG Blockers:	0.015	hERG Blockers (10um):	0.082
Human Hepatotoxicity (H-HT):	0.793	Drug-induced Liver Injury (DILI):	0.148
AMES Toxicity:	0.068	Rat Oral Acute Toxicity:	0.118
Maximum Recommended Daily Dose:	0.315	Skin Sensitization:	0.802
Carcinogencity:	0.484	Eye Corrosion:	0.064
Eye Irritation:	0.916	Respiratory Toxicity:	0.332
Drug-induced Neurotoxicity:	0.123	Ototoxicity:	0.624
Hematotoxicity:	0.166	Drug-induced Nephrotoxicity:	0.789
Genotoxicity:	0.004	RPMI-8226 Immunitoxicity:	0.02
A549 Cytotoxicity:	0.005	Hek293 Cytotoxicity:	0.089
BCF:	1.494 ? 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:	4.194 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.578 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.832 ? 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
NPO21387	Forsythia suspensa	Species	Oleaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[17156960]
NPO21387	Forsythia suspensa	Species	Oleaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[26422318]
NPO21387	Forsythia suspensa	Species	Oleaceae	Eukaryota	Fruits	n.a.	n.a.	PMID[28218000]
NPO21387	Forsythia suspensa	Species	Oleaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO21387	Forsythia suspensa	Species	Oleaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO21387	Forsythia suspensa	Species	Oleaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO21387	Forsythia suspensa	Species	Oleaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO21387	Forsythia suspensa	Species	Oleaceae	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	2
Inhibition	1

Activity Type	# Activity
Cell line	3

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
NPT2740	Cell line	Neutrophils	n.a.	IC50	=	7.4	ug.mL-1	PMID[28218000]
NPT2740	Cell line	Neutrophils	n.a.	IC50	>	10.0	ug.mL-1	PMID[28218000]
NPT2740	Cell line	Neutrophils	n.a.	Inhibition	>	50.0	%	PMID[28218000]

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 NPC488504 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	21363
0.1-0.2	24772
0.2-0.3	3366
0.3-0.4	280
0.4-0.5	50
0.5-0.6	13
0.6-0.7	10
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC194322
1.0	High Similarity	NPC488496
0.7609	Intermediate Similarity	NPC107258
0.6731	Remote Similarity	NPC488500
0.6667	Remote Similarity	NPC281880
0.6471	Remote Similarity	NPC2524
0.6364	Remote Similarity	NPC488497
0.625	Remote Similarity	NPC481631
0.62	Remote Similarity	NPC481628
0.6154	Remote Similarity	NPC133253
0.6122	Remote Similarity	NPC143765
0.6038	Remote Similarity	NPC159148
0.6	Remote Similarity	NPC69649
0.5849	Remote Similarity	NPC488498
0.5849	Remote Similarity	NPC132542
0.5849	Remote Similarity	NPC61952
0.5849	Remote Similarity	NPC603184
0.58	Remote Similarity	NPC476406
0.5714	Remote Similarity	NPC170303
0.5636	Remote Similarity	NPC106416
0.5636	Remote Similarity	NPC86316
0.5636	Remote Similarity	NPC609165
0.549	Remote Similarity	NPC149680
0.549	Remote Similarity	NPC600344
0.537	Remote Similarity	NPC259156
0.5357	Remote Similarity	NPC476601

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC488504 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5712
0.1-0.2	3299
0.2-0.3	135
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