NPASS Compound

Natural Product: NPC485313

Natural Product ID	NPC485313
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	OBSYBRPAKCASQB-ASUQIVHDSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	11546512
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001283] Terpene lactones [CHEMONTID:0001538] Diterpene lactones

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 59 62 0 0 0 0 0 0 0 0999 V2000 2.8362 5.0687 1.4459 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7658 3.5777 1.5704 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3228 3.0790 2.5848 O 0 0 0 0 0 0 0 0 0 0 0 0 2.1271 2.7931 0.6278 O 0 0 0 0 0 0 0 0 0 0 0 0 2.0856 1.3841 0.7872 C 0 0 2 0 0 0 0 0 0 0 0 0 2.6911 0.8011 -0.4520 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3883 -0.6208 -0.7184 C 0 0 1 0 0 0 0 0 0 0 0 0 3.5629 -1.4686 -0.3990 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6388 -0.9606 0.0687 O 0 0 0 0 0 0 0 0 0 0 0 0 3.5939 -2.8435 -0.5760 O 0 0 0 0 0 0 0 0 0 0 0 0 4.7224 -3.6363 -0.2671 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1136 -1.1204 -0.0765 C 0 0 2 0 0 0 0 0 0 0 0 0 1.4967 -1.7443 1.2441 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5904 -2.2674 -0.9533 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7839 -2.7043 -0.5814 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6898 -1.5041 -0.6864 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.1127 -1.8311 -0.4487 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5547 -2.9964 -0.7305 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.9239 -0.8484 0.0778 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.6069 0.5372 0.0974 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.1560 0.7973 -0.1353 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2921 -0.4057 0.2731 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.6343 -0.7374 1.6871 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1233 -0.0118 0.0210 C 0 0 1 0 0 0 0 0 0 0 0 0 0.6292 1.0295 0.9201 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0081 1.6406 1.7610 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.4733 1.1686 -0.9299 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1756 2.3369 -0.7601 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8524 2.5829 -1.9403 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5753 1.6138 -2.7832 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.7583 0.7552 -2.2166 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9685 5.5623 1.9103 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7427 5.4852 1.9163 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8371 5.3749 0.3771 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6100 1.1303 1.7072 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4367 1.4543 -1.3383 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8020 0.9194 -0.3500 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2433 -0.7331 -1.8346 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5209 -3.5503 -1.0324 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3787 -4.7009 -0.2499 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1180 -3.3997 0.7376 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6704 -1.9320 1.9272 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3662 -1.2449 1.7256 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8957 -2.7745 0.9959 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5642 -1.9491 -2.0281 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2925 -3.0967 -0.8621 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1189 -3.4266 -1.3538 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8546 -3.2151 0.3876 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5583 -1.0946 -1.7138 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8626 0.9780 1.0887 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0139 0.8673 -1.2525 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7896 1.7336 0.2752 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9880 -0.3232 2.4586 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6756 -0.4081 1.9834 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7152 -1.8639 1.7402 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1208 0.4665 -1.0124 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2194 2.9767 0.1165 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4947 3.4294 -2.1239 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3839 -0.1296 -2.7074 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 2 0 8 10 1 0 10 11 1 0 7 12 1 0 12 13 1 1 12 14 1 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 2 0 17 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 1 1 22 24 1 0 24 25 1 0 25 26 2 0 20 27 1 0 27 28 1 0 28 29 2 0 29 30 1 0 30 31 1 0 25 5 1 0 31 27 2 0 24 12 1 0 22 16 1 0 1 32 1 0 1 33 1 0 1 34 1 0 5 35 1 1 6 36 1 0 6 37 1 0 7 38 1 6 11 39 1 0 11 40 1 0 11 41 1 0 13 42 1 0 13 43 1 0 13 44 1 0 14 45 1 0 14 46 1 0 15 47 1 0 15 48 1 0 16 49 1 6 20 50 1 1 21 51 1 0 21 52 1 0 23 53 1 0 23 54 1 0 23 55 1 0 24 56 1 6 28 57 1 0 29 58 1 0 31 59 1 0 M END

Standard InCHIKey	OBSYBRPAKCASQB-ASUQIVHDSA-N
Standard InCHI	InChI=1S/C23H28O8/c1-12(24)30-16-9-15(20(26)28-4)22(2)7-5-14-21(27)31-17(13-6-8-29-11-13)10-23(14,3)19(22)18(16)25/h6,8,11,14-17,19H,5,7,9-10H2,1-4H3/t14-,15-,16+,17-,19-,22-,23-/m0/s1
SMILES	CC(=O)O[C@@H]1C[C@@H](C(=O)OC)[C@]2(C)CC[C@H]3C(=O)O[C@@H](C[C@]3(C)[C@H]2C1=O)c1ccoc1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	432.18	Volume:	426.641 ? Van der Waals volume.
Dense:	1.013	LogP:	1.659 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.903 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.632 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	25.0
TPSA:	109.11 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	0.0	Rings:	4.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.53	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.625	Fsp³:	0.652
MCE-18:	100.211 ? 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:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.452	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.015 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.001 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.203	Promiscuous compounds:	0.206

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.955	MDCK Permeability:	-4.743
Pgp-inhibitor:	0.936	Pgp-substrate:	0.057
PAMPA:	0.163 ? 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):	0.017
20% Bioavailability (F20%):	0.12	30% Bioavailability (F30%):	0.459
50% Bioavailability (F50%):	0.754

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.744
Plasma Protein Binding (PPB):	47.894%	Volume Distribution (VD):	-0.014
Fu:	52.391% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.997	BCRP inhibitor:	0.113
BSEP inhibitor:	0.993

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.978
CYP2C19-inhibitor:	0.991	CYP2C19-substrate:	0.001
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.498
CYP3A4-inhibitor:	0.997	CYP3A4-substrate:	0.213
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.994
HLM stability:	0.864 ? 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):

6.106

Half-life (T1/2):

1.112

ADMET: Toxicity

hERG Blockers:	0.043	hERG Blockers (10um):	0.114
Human Hepatotoxicity (H-HT):	0.901	Drug-induced Liver Injury (DILI):	0.989
AMES Toxicity:	0.729	Rat Oral Acute Toxicity:	0.789
Maximum Recommended Daily Dose:	0.891	Skin Sensitization:	0.853
Carcinogencity:	0.926	Eye Corrosion:	0.001
Eye Irritation:	0.465	Respiratory Toxicity:	0.188
Drug-induced Neurotoxicity:	0.333	Ototoxicity:	0.236
Hematotoxicity:	0.204	Drug-induced Nephrotoxicity:	0.925
Genotoxicity:	0.999	RPMI-8226 Immunitoxicity:	0.082
A549 Cytotoxicity:	0.269	Hek293 Cytotoxicity:	0.143
BCF:	1.043 ? 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:	3.767 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.962 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.367 ? 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
NPO634	Salvia divinorum	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[14510607]
NPO634	Salvia divinorum	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[15987194]
NPO634	Salvia divinorum	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[16441078]
NPO634	Salvia divinorum	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[16621556]
NPO634	Salvia divinorum	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[16945525]
NPO634	Salvia divinorum	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[17190459]
NPO634	Salvia divinorum	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[17580847]
NPO634	Salvia divinorum	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[21338114]
NPO634	Salvia divinorum	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[25193297]
NPO634	Salvia divinorum	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[36987013]
NPO634	Salvia divinorum	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO634	Salvia divinorum	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
Ki	1
EC50	5
Ratio EC50	3

Activity Type	# Activity
Individual protein	8
Others	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	Ki	=	424.0	nM	PMID[16777411]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	EC50	=	306.0	nM	PMID[16777411]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	Ratio EC50	=	1.0	n.a.	PMID[16441078]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	Ratio EC50	=	1.9	n.a.	PMID[16441078]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	EC50	=	385.0	nM	PMID[16441078]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	EC50	=	6.5	nM	PMID[16441078]
NPT145	Individual protein	Mu opioid receptor	Homo sapiens	EC50	>	10000.0	nM	PMID[27958743]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	EC50	=	110.0	nM	PMID[27958743]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT2	Others	Unspecified	n.a.	Ratio EC50	<	1.1	10^-2No_unit	PMID[27958743]

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 NPC485313 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	13364
0.1-0.2	35058
0.2-0.3	1153
0.3-0.4	232
0.4-0.5	33
0.5-0.6	9
0.6-0.7	5
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	NPC262198
0.75	Intermediate Similarity	NPC485320
0.6765	Remote Similarity	NPC601789
0.6623	Remote Similarity	NPC485321
0.6538	Remote Similarity	NPC485322
0.6301	Remote Similarity	NPC485323
0.6027	Remote Similarity	NPC485324
0.5797	Remote Similarity	NPC476943
0.5641	Remote Similarity	NPC606944
0.5584	Remote Similarity	NPC610593
0.5443	Remote Similarity	NPC610061
0.5333	Remote Similarity	NPC310830
0.5325	Remote Similarity	NPC18347
0.527	Remote Similarity	NPC608381
0.527	Remote Similarity	NPC609872
0.5205	Remote Similarity	NPC606229

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC485313 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3824
0.1-0.2	5274
0.2-0.3	52
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