NPASS Compound

Natural Product: NPC561924

Natural Product ID	NPC561924
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	6R,8R-dihydroxy-9Z,12Z-octadecadienoic acid
IUPAC Name	(6~{R},8~{R},9~{Z},12~{Z})-6,8-dihydroxyoctadeca-9,12-dienoic acid
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:0003909] Fatty Acyls [CHEMONTID:0000504] Lineolic acids 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 54 53 0 0 0 0 0 0 0 0999 V2000 -8.5808 -0.8006 -0.0772 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.4219 0.1661 -0.3590 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.5523 0.1434 0.8734 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3623 1.0532 0.7512 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4530 0.6804 -0.4221 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9828 -0.6971 -0.1860 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7100 -0.9874 -0.0694 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6022 -0.0097 -0.1554 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8876 -0.0646 1.1434 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3841 -0.3854 1.1831 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0851 -0.6866 -0.0720 C 0 0 2 0 0 0 0 0 0 0 0 0 0.7028 -1.9570 -0.5661 O 0 0 0 0 0 0 0 0 0 0 0 0 2.5713 -0.7600 0.2140 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1249 0.5307 0.7747 C 0 0 2 0 0 0 0 0 0 0 0 0 2.9727 1.6246 -0.0570 O 0 0 0 0 0 0 0 0 0 0 0 0 4.5149 0.3656 1.2764 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5387 -0.0885 0.2919 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6867 0.8655 -0.8522 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7335 0.4004 -1.8218 C 0 0 0 0 0 0 0 0 0 0 0 0 8.0538 0.3602 -1.2015 C 0 0 0 0 0 0 0 0 0 0 0 0 8.2621 0.7839 -0.0558 O 0 0 0 0 0 0 0 0 0 0 0 0 9.1189 -0.1734 -1.9239 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.2572 -1.6331 0.5777 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.3147 -0.2044 0.5054 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.0150 -1.1986 -1.0054 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8458 -0.3328 -1.1756 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.7873 1.1608 -0.6254 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2748 -0.9074 1.0732 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1386 0.4649 1.7731 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7185 1.0071 1.6502 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7105 2.0983 0.6621 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7065 1.4529 -0.4935 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1131 0.7133 -1.3474 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7394 -1.5250 -0.1043 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4706 -2.0677 0.1091 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8927 1.0063 -0.4324 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9591 -0.3926 -0.9927 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4447 0.1656 2.0412 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9509 -0.4400 2.1191 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9819 0.0654 -0.8687 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5308 -2.5853 0.1642 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1556 -0.9560 -0.7282 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7217 -1.5493 0.9618 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5105 0.8130 1.7013 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4257 1.4753 -0.8406 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8231 1.3589 1.7075 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4706 -0.3402 2.1492 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1607 -1.0812 -0.1098 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5010 -0.2244 0.7861 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0118 1.8617 -0.4321 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7189 1.0666 -1.3741 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3988 -0.6319 -2.1597 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7362 1.0378 -2.7522 H 0 0 0 0 0 0 0 0 0 0 0 0 10.0936 -0.0413 -1.6355 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 2 0 7 8 1 0 8 9 1 0 9 10 2 0 10 11 1 0 11 12 1 0 11 13 1 0 13 14 1 0 14 15 1 0 14 16 1 0 16 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 2 0 20 22 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 7 35 1 0 8 36 1 0 8 37 1 0 9 38 1 0 10 39 1 0 11 40 1 6 12 41 1 0 13 42 1 0 13 43 1 0 14 44 1 1 15 45 1 0 16 46 1 0 16 47 1 0 17 48 1 0 17 49 1 0 18 50 1 0 18 51 1 0 19 52 1 0 19 53 1 0 22 54 1 0 M END

Standard InCHIKey	JEJFTAIQLBEZLI-PIEIVNQGSA-N
Standard InCHI	InChI=1S/C18H32O4/c1-2-3-4-5-6-7-8-9-12-16(19)15-17(20)13-10-11-14-18(21)22/h6-7,9,12,16-17,19-20H,2-5,8,10-11,13-15H2,1H3,(H,21,22)/b7-6-,12-9-/t16-,17+/m0/s1
SMILES	CCCCC/C=CC/C=C[C@H](O)C[C@H](O)CCCCC(=O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	312.23	Volume:	347.136 ? Van der Waals volume.
Dense:	0.899	LogP:	3.98 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.04 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.614 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	14.0	Rigid Bonds:	3.0
TPSA:	77.76 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	3.0	Rings:	0.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.336	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.351	Fsp³:	0.722
MCE-18:	3.0 ? 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:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.049	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.004 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.0 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.932	Promiscuous compounds:	0.885

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.213	MDCK Permeability:	-4.95
Pgp-inhibitor:	0.002	Pgp-substrate:	0.01
PAMPA:	0.431 ? 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):	0.025
20% Bioavailability (F20%):	0.088	30% Bioavailability (F30%):	0.398
50% Bioavailability (F50%):	0.594

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.173	MRP1:	0.987
Plasma Protein Binding (PPB):	95.497%	Volume Distribution (VD):	-0.435
Fu:	4.459% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.088
OATP1B3 inhibitor:	0.895	BCRP inhibitor:	0.083
BSEP inhibitor:	0.606

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.002	CYP2C19-substrate:	0.027
CYP2C9-inhibitor:	1.0	CYP2C9-substrate:	0.102
CYP2D6-inhibitor:	0.003	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.999
HLM stability:	0.067 ? 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):

7.916

Half-life (T1/2):

0.851

ADMET: Toxicity

hERG Blockers:	0.15	hERG Blockers (10um):	0.208
Human Hepatotoxicity (H-HT):	0.166	Drug-induced Liver Injury (DILI):	0.001
AMES Toxicity:	0.185	Rat Oral Acute Toxicity:	0.072
Maximum Recommended Daily Dose:	0.164	Skin Sensitization:	1.0
Carcinogencity:	0.022	Eye Corrosion:	0.992
Eye Irritation:	0.996	Respiratory Toxicity:	0.965
Drug-induced Neurotoxicity:	0.033	Ototoxicity:	0.628
Hematotoxicity:	0.022	Drug-induced Nephrotoxicity:	0.806
Genotoxicity:	0.0	RPMI-8226 Immunitoxicity:	0.035
A549 Cytotoxicity:	0.671	Hek293 Cytotoxicity:	0.079
BCF:	0.689 ? 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:	3.447 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.63 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.436 ? 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
NPO51219	Penicillium javanicum HK1-22	Genus	Aspergillaceae	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

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 NPC561924 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	29546
0.1-0.2	18514
0.2-0.3	1504
0.3-0.4	165
0.4-0.5	82
0.5-0.6	32
0.6-0.7	12
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
0.6531	Remote Similarity	NPC323045
0.6531	Remote Similarity	NPC317881
0.6429	Remote Similarity	NPC321062
0.6429	Remote Similarity	NPC5413
0.6279	Remote Similarity	NPC154245
0.6279	Remote Similarity	NPC85813
0.6279	Remote Similarity	NPC223697
0.6279	Remote Similarity	NPC6095
0.625	Remote Similarity	NPC243532
0.6087	Remote Similarity	NPC606120
0.6047	Remote Similarity	NPC91495
0.6	Remote Similarity	NPC327112
0.5962	Remote Similarity	NPC605544
0.5962	Remote Similarity	NPC607260
0.5918	Remote Similarity	NPC255863
0.5918	Remote Similarity	NPC136164
0.5918	Remote Similarity	NPC245947
0.5909	Remote Similarity	NPC59051
0.5682	Remote Similarity	NPC70387
0.5581	Remote Similarity	NPC424
0.5581	Remote Similarity	NPC36061
0.5581	Remote Similarity	NPC69510
0.5581	Remote Similarity	NPC77272
0.5581	Remote Similarity	NPC290563
0.5581	Remote Similarity	NPC139029
0.5581	Remote Similarity	NPC281972
0.5581	Remote Similarity	NPC92114
0.5581	Remote Similarity	NPC261831
0.5581	Remote Similarity	NPC87564
0.5577	Remote Similarity	NPC49863
0.5556	Remote Similarity	NPC52955
0.5556	Remote Similarity	NPC88966
0.5556	Remote Similarity	NPC25417
0.5556	Remote Similarity	NPC1813
0.549	Remote Similarity	NPC321838
0.5455	Remote Similarity	NPC149821
0.5349	Remote Similarity	NPC281245
0.5333	Remote Similarity	NPC324004
0.5333	Remote Similarity	NPC328497
0.5111	Remote Similarity	NPC95145
0.5111	Remote Similarity	NPC325642
0.5111	Remote Similarity	NPC207292
0.5111	Remote Similarity	NPC65174
0.5094	Remote Similarity	NPC320642

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC561924 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6585
0.1-0.2	2356
0.2-0.3	165
0.3-0.4	22
0.4-0.5	13
0.5-0.6	6
0.6-0.7	3
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
0.6429	Remote Similarity	NPD3173	Phase 4
0.6279	Remote Similarity	NPD4266	Phase 2
0.6	Remote Similarity	NPD4246	Phase 2
0.5581	Remote Similarity	NPD3195	Phase 2
0.5581	Remote Similarity	NPD3196	Approved
0.5577	Remote Similarity	NPD4247	Clinical (unspecified phase)
0.5556	Remote Similarity	NPD3172	Approved
0.5417	Remote Similarity	NPD3194	Phase 4
0.5192	Remote Similarity	NPD39	Phase 4

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