NPASS Compound

Natural Product: NPC327247

Natural Product ID	NPC327247
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	FWBSIMCZPHJUNZ-SPYHJPNNSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	70698225
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001551] Diterpenoids [CHEMONTID:0003782] Kaurane 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 60 63 0 0 0 0 0 0 0 0999 V2000 -0.6338 5.1796 -0.1943 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9005 3.9463 0.6001 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2232 4.1159 1.8051 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8162 2.6802 0.1062 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.0825 1.5202 0.9097 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8876 0.2623 0.0126 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5192 0.3194 -0.4370 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7630 -0.0653 -1.9001 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1854 0.4236 -2.2219 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1767 0.0472 -1.1708 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5967 -1.0863 -0.3594 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5355 -0.3016 0.4375 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0957 -1.1828 1.5253 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3095 -1.0645 1.9678 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3206 -0.8700 0.8648 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8288 -2.1140 0.2731 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8843 -1.7951 -0.7637 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3412 -0.8083 -1.7433 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8992 0.4648 -1.0863 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0653 1.0062 -0.4850 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.6324 -2.8190 1.3966 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9101 -3.1473 -0.2196 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8958 -0.9987 2.6848 O 0 0 0 0 0 0 0 0 0 0 0 0 2.4839 0.7298 1.0226 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5059 1.1400 2.1993 O 0 0 0 0 0 0 0 0 0 0 0 0 3.3213 1.0900 -0.1189 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0641 2.1818 -0.1472 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5159 -1.5467 0.6005 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.4429 5.9087 0.0686 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3174 5.6438 0.0610 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7547 4.9534 -1.2703 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1104 1.6085 1.2516 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3616 1.5447 1.7238 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8028 1.4240 -0.5065 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7518 -1.1218 -2.1027 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1124 0.4501 -2.5966 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1313 1.5491 -2.2802 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4985 0.0818 -3.2120 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1561 -0.2852 -1.5744 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2011 -1.9138 -0.9215 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2701 -2.2757 1.2834 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6035 -1.9897 2.5137 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3935 -0.2390 2.7026 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2290 -0.4763 1.4398 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1776 -2.7088 -1.3369 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7989 -1.4565 -0.2483 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6174 -1.2821 -2.3958 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2102 -0.5184 -2.4088 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6171 1.2021 -1.8451 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8761 0.7148 -0.9544 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4146 -3.4479 0.9530 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9437 -3.5082 1.9538 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9943 -2.0896 2.1324 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0260 -2.8682 -0.6724 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4641 -3.7583 -0.9963 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6528 -3.9226 0.5647 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5695 -1.6428 3.3886 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1104 2.8816 0.6556 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6760 2.4095 -1.0256 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1153 -2.1745 0.0967 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 2 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 16 21 1 0 16 22 1 0 13 23 1 0 12 24 1 0 24 25 2 0 24 26 1 0 26 27 2 0 11 28 1 0 15 6 1 0 19 6 1 0 12 7 1 0 26 10 1 0 1 29 1 0 1 30 1 0 1 31 1 0 5 32 1 0 5 33 1 0 7 34 1 0 8 35 1 0 8 36 1 0 9 37 1 0 9 38 1 0 10 39 1 0 11 40 1 0 13 41 1 0 14 42 1 0 14 43 1 0 15 44 1 0 17 45 1 0 17 46 1 0 18 47 1 0 18 48 1 0 19 49 1 0 20 50 1 0 21 51 1 0 21 52 1 0 21 53 1 0 22 54 1 0 22 55 1 0 22 56 1 0 23 57 1 0 27 58 1 0 27 59 1 0 28 60 1 0 M END

Standard InCHIKey	FWBSIMCZPHJUNZ-SPYHJPNNSA-N
Standard InCHI	InChI=1S/C22H32O6/c1-11-13-5-6-14-21(10-28-12(2)23)15(20(3,4)8-7-16(21)24)9-17(25)22(14,18(11)26)19(13)27/h13-17,19,24-25,27H,1,5-10H2,2-4H3/t13-,14+,15-,16+,17-,19-,21+,22+/m1/s1
SMILES	CC(=O)OCC12C3CCC4C(C3(C(CC1C(CCC2O)(C)C)O)C(=O)C4=C)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	392.22	Volume:	399.674 ? Van der Waals volume.
Dense:	0.981	LogP:	1.512 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.939 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.495 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	22.0
TPSA:	104.06 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	3.0	Rings:	4.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.487	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	6.087	Fsp³:	0.818
MCE-18:	111.0 ? 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:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.01	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.025 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.04 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.226	Promiscuous compounds:	0.008

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.276	MDCK Permeability:	-5.039
Pgp-inhibitor:	0.025	Pgp-substrate:	0.851
PAMPA:	0.995 ? 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):	0.871
20% Bioavailability (F20%):	0.73	30% Bioavailability (F30%):	0.964
50% Bioavailability (F50%):	0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.004	MRP1:	0.921
Plasma Protein Binding (PPB):	22.803%	Volume Distribution (VD):	-0.115
Fu:	74.752% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.897
OATP1B3 inhibitor:	0.993	BCRP inhibitor:	0.003
BSEP inhibitor:	0.522

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.034	CYP2C19-substrate:	0.003
CYP2C9-inhibitor:	0.153	CYP2C9-substrate:	0.001
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.001
CYP3A4-inhibitor:	0.145	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.455
HLM stability:	0.211 ? 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):

6.877

Half-life (T1/2):

1.998

ADMET: Toxicity

hERG Blockers:	0.058	hERG Blockers (10um):	0.301
Human Hepatotoxicity (H-HT):	0.724	Drug-induced Liver Injury (DILI):	0.634
AMES Toxicity:	0.603	Rat Oral Acute Toxicity:	0.411
Maximum Recommended Daily Dose:	0.943	Skin Sensitization:	0.041
Carcinogencity:	0.53	Eye Corrosion:	0.0
Eye Irritation:	0.003	Respiratory Toxicity:	0.504
Drug-induced Neurotoxicity:	0.442	Ototoxicity:	0.945
Hematotoxicity:	0.181	Drug-induced Nephrotoxicity:	0.134
Genotoxicity:	0.847	RPMI-8226 Immunitoxicity:	0.188
A549 Cytotoxicity:	0.089	Hek293 Cytotoxicity:	0.718
BCF:	0.471 ? 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:	3.571 ? 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:	4.333 ? 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
NPO1927	Isodon eriocalyx	Species	Lamiaceae	Eukaryota	n.a.	leaf	n.a.	PMID[17020288]
NPO1927	Isodon eriocalyx	Species	Lamiaceae	Eukaryota	n.a.	aerial part	n.a.	PMID[20949916]
NPO1927	Isodon eriocalyx	Species	Lamiaceae	Eukaryota	aerial parts	n.a.	n.a.	PMID[20949916]
NPO1927	Isodon eriocalyx	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[22624550]
NPO1927	Isodon eriocalyx	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO1927	Isodon eriocalyx	Species	Lamiaceae	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

Activity Type	# Activity
Cell line	1
Unchecked	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
NPT660	Cell line	SW480	Homo sapiens	IC50	=	16780.0	nM	PMID[33445154]
NPT28438	Unchecked	Unchecked	n.a.	IC50	=	600.0	nM	PMID[36183504]

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 NPC327247 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	17141
0.1-0.2	27389
0.2-0.3	4985
0.3-0.4	254
0.4-0.5	58
0.5-0.6	20
0.6-0.7	9
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC52899
0.6964	Remote Similarity	NPC163963
0.6923	Remote Similarity	NPC181594
0.6667	Remote Similarity	NPC144739
0.6379	Remote Similarity	NPC16911
0.6271	Remote Similarity	NPC287676
0.6111	Remote Similarity	NPC261994
0.6111	Remote Similarity	NPC470378
0.6034	Remote Similarity	NPC289148
0.6	Remote Similarity	NPC165895
0.5574	Remote Similarity	NPC87927
0.5574	Remote Similarity	NPC475803
0.5536	Remote Similarity	NPC138245
0.55	Remote Similarity	NPC78427
0.5439	Remote Similarity	NPC299185
0.5357	Remote Similarity	NPC111524
0.5345	Remote Similarity	NPC180849
0.5345	Remote Similarity	NPC149761
0.5323	Remote Similarity	NPC309388
0.5254	Remote Similarity	NPC59350
0.5246	Remote Similarity	NPC214946
0.5238	Remote Similarity	NPC474558
0.5231	Remote Similarity	NPC488143
0.5161	Remote Similarity	NPC148628
0.5152	Remote Similarity	NPC488142
0.5152	Remote Similarity	NPC213320
0.5079	Remote Similarity	NPC55973
0.5079	Remote Similarity	NPC89860
0.5079	Remote Similarity	NPC189663
0.5079	Remote Similarity	NPC153234

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC327247 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6023
0.1-0.2	3007
0.2-0.3	120
0.3-0.4	0
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