NPASS Compound

Natural Product: NPC137066

Natural Product ID	NPC137066
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	KGMSWPSAVZAMKR-TWZMTFLISA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	90472509
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 52 54 0 0 0 0 0 0 0 0999 V2000 4.9428 0.0425 1.7890 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4436 -0.1588 0.3927 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2146 0.1629 0.0517 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7988 -0.0690 -1.3551 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4012 -0.6334 -1.2954 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5025 0.4461 -0.6796 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9556 0.8698 0.6301 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2264 0.7390 0.9791 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0484 1.4760 1.6264 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3668 1.6133 1.0611 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6648 0.2673 0.4561 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.9237 0.0054 -0.7990 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.5132 0.6676 -2.0214 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0517 -1.4979 -1.0383 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4969 -1.8638 -1.1863 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4233 -1.3591 -0.1572 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1485 -0.0015 0.4047 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.9324 1.0883 -0.2763 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5961 -0.0345 1.8279 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4560 0.7567 2.2837 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.0540 -0.9669 2.6968 O 0 0 0 0 0 0 0 0 0 0 0 0 5.3877 -0.7337 -0.5873 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6340 1.0935 2.0587 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4708 -0.6780 2.4624 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0495 0.0411 1.8132 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4999 -0.7218 -1.8967 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7203 0.9284 -1.8387 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0829 -0.7096 -2.3761 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3516 -1.5793 -0.7599 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6788 1.3342 -1.3689 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5983 1.0424 1.9448 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3653 2.4941 1.9288 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0504 0.8632 2.5434 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0391 1.7547 1.9342 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4533 2.4517 0.3741 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2793 -0.4873 1.2114 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5259 0.3627 -2.2707 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8697 0.3211 -2.8856 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3572 1.7810 -2.0163 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6239 -2.0628 -0.1896 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5403 -1.8217 -1.9490 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8855 -1.6389 -2.2235 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5310 -2.9953 -1.1539 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5486 -2.1321 0.6578 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4543 -1.3083 -0.6193 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5867 0.6596 -1.0891 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6817 1.5749 0.4173 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3099 1.9292 -0.6353 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0582 -0.7414 3.6797 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4198 -0.7239 -0.2035 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3867 -0.0717 -1.4825 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1420 -1.7764 -0.8704 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 1 0 7 8 2 0 7 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 6 12 14 1 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 1 6 17 19 1 0 19 20 2 0 19 21 1 0 2 22 1 0 8 3 1 0 17 11 1 0 12 6 1 0 1 23 1 0 1 24 1 0 1 25 1 0 4 26 1 0 4 27 1 0 5 28 1 0 5 29 1 0 6 30 1 0 8 31 1 0 9 32 1 0 9 33 1 0 10 34 1 0 10 35 1 0 11 36 1 1 13 37 1 0 13 38 1 0 13 39 1 0 14 40 1 0 14 41 1 0 15 42 1 0 15 43 1 0 16 44 1 0 16 45 1 0 18 46 1 0 18 47 1 0 18 48 1 0 21 49 1 0 22 50 1 0 22 51 1 0 22 52 1 0 M END

Standard InCHIKey	KGMSWPSAVZAMKR-TWZMTFLISA-N
Standard InCHI	InChI=1S/C20H30O2/c1-13(2)14-6-8-16-15(12-14)7-9-17-19(16,3)10-5-11-20(17,4)18(21)22/h12,16-17H,5-11H2,1-4H3,(H,21,22)/t16?,17-,19-,20-/m1/s1
SMILES	CC(=C1CCC2C(=C1)CC[C@@H]1[C@]2(C)CCC[C@@]1(C)C(=O)O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	302.22	Volume:	338.478 ? Van der Waals volume.
Dense:	0.893	LogP:	3.916 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.044 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.955 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	1.0	Rigid Bonds:	18.0
TPSA:	37.3 ? Topological Polar Surface Area.	H-Bond Acceptor:	2.0
H-Bond Donor:	1.0	Rings:	3.0
Heavy Atoms:	2.0

MedChem Properties

QED Drug-Likeness Score:	0.709	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.217	Fsp³:	0.75
MCE-18:	55.2 ? 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:	0.18	Fluc inhibitor:	0.008 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.01 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.075 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.814	Promiscuous compounds:	0.061

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.644	MDCK Permeability:	-4.73
Pgp-inhibitor:	0.095	Pgp-substrate:	0.006
PAMPA:	0.453 ? 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%):	0.046	30% Bioavailability (F30%):	0.014
50% Bioavailability (F50%):	0.366

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.175	MRP1:	0.976
Plasma Protein Binding (PPB):	97.37%	Volume Distribution (VD):	-0.401
Fu:	3.463% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.997
OATP1B3 inhibitor:	0.987	BCRP inhibitor:	0.028
BSEP inhibitor:	0.959

ADMET: Metabolism

CYP1A2-inhibitor:	0.054	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.034	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.996	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.001	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.883	CYP3A4-substrate:	0.007
CYP2B6-substrate:	0.035	CYP2C8-inhibitor:	0.093
HLM stability:	0.002 ? 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):

3.863

Half-life (T1/2):

1.124

ADMET: Toxicity

hERG Blockers:	0.066	hERG Blockers (10um):	0.285
Human Hepatotoxicity (H-HT):	0.806	Drug-induced Liver Injury (DILI):	0.507
AMES Toxicity:	0.101	Rat Oral Acute Toxicity:	0.179
Maximum Recommended Daily Dose:	0.597	Skin Sensitization:	0.965
Carcinogencity:	0.92	Eye Corrosion:	0.776
Eye Irritation:	0.98	Respiratory Toxicity:	0.85
Drug-induced Neurotoxicity:	0.391	Ototoxicity:	0.432
Hematotoxicity:	0.304	Drug-induced Nephrotoxicity:	0.555
Genotoxicity:	0.066	RPMI-8226 Immunitoxicity:	0.024
A549 Cytotoxicity:	0.032	Hek293 Cytotoxicity:	0.146
BCF:	1.673 ? 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:	4.371 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.61 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.155 ? 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
NPO12422	Pinus massoniana	Species	Pinaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[32100544]
NPO12422	Pinus massoniana	Species	Pinaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12422	Pinus massoniana	Species	Pinaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO12422	Pinus massoniana	Species	Pinaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO12422	Pinus massoniana	Species	Pinaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO12422	Pinus massoniana	Species	Pinaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO12422	Pinus massoniana	Species	Pinaceae	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 NPC137066 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	26831
0.1-0.2	21089
0.2-0.3	1711
0.3-0.4	111
0.4-0.5	78
0.5-0.6	31
0.6-0.7	8
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
0.6863	Remote Similarity	NPC109854
0.6667	Remote Similarity	NPC161923
0.6667	Remote Similarity	NPC183503
0.6667	Remote Similarity	NPC283908
0.6667	Remote Similarity	NPC103958
0.6667	Remote Similarity	NPC610917
0.6538	Remote Similarity	NPC165711
0.6296	Remote Similarity	NPC610334
0.5849	Remote Similarity	NPC488498
0.5849	Remote Similarity	NPC61952
0.5849	Remote Similarity	NPC481630
0.5849	Remote Similarity	NPC603184
0.5741	Remote Similarity	NPC198240
0.5741	Remote Similarity	NPC237591
0.5741	Remote Similarity	NPC3753
0.5714	Remote Similarity	NPC239098
0.5636	Remote Similarity	NPC59436
0.5536	Remote Similarity	NPC471159
0.5536	Remote Similarity	NPC123880
0.5536	Remote Similarity	NPC18819
0.5536	Remote Similarity	NPC46610
0.5517	Remote Similarity	NPC40228
0.55	Remote Similarity	NPC479671
0.5455	Remote Similarity	NPC72343
0.5455	Remote Similarity	NPC36616
0.5439	Remote Similarity	NPC269543
0.5439	Remote Similarity	NPC247783
0.5424	Remote Similarity	NPC600691
0.5397	Remote Similarity	NPC606907
0.5357	Remote Similarity	NPC192540
0.5273	Remote Similarity	NPC99154
0.5263	Remote Similarity	NPC91369
0.5246	Remote Similarity	NPC14203
0.5246	Remote Similarity	NPC229584
0.5246	Remote Similarity	NPC477782
0.5231	Remote Similarity	NPC610335
0.5167	Remote Similarity	NPC232344
0.5161	Remote Similarity	NPC477783
0.5085	Remote Similarity	NPC483605

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC137066 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6460
0.1-0.2	2565
0.2-0.3	124
0.3-0.4	0
0.4-0.5	1
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