NPASS Compound

Natural Product: NPC481022

Natural Product ID	NPC481022
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	KUSFVCHTPOSQLS-SWSYEKRDSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	127041378
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001551] Diterpenoids [CHEMONTID:0001757] Colensane and clerodane 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 64 66 0 0 0 0 0 0 0 0999 V2000 5.5792 -1.0856 -2.0336 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5900 -0.1006 -1.1724 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4319 0.7185 -0.8522 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5952 1.6826 0.0399 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1474 0.4686 -1.4719 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8758 0.7817 -0.8294 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2944 0.1147 0.3365 C 0 0 2 0 0 0 0 0 0 0 0 0 2.2606 0.2105 1.5287 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0503 -1.3592 0.2747 C 0 0 2 0 0 0 0 0 0 0 0 0 2.1471 -2.1550 -0.3890 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2363 -1.8232 -0.3036 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3878 -1.2166 0.4194 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.2703 0.3053 0.1490 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.4021 1.0156 0.8920 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4007 1.3098 2.1470 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2746 0.9830 3.0042 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.0791 0.5371 2.2690 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0417 0.7934 0.7539 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.9297 2.1135 3.7991 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.4391 1.3271 -0.1829 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.2962 2.3215 0.2066 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.6219 1.8911 0.2185 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5121 1.7643 -1.1463 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.7710 0.5218 -1.1802 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.1769 0.3781 -2.3535 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.8293 -0.4044 -3.3016 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5696 -1.6765 -0.1698 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.3716 -2.3304 0.7610 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5038 -1.6590 -2.2188 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7438 -1.4178 -2.6084 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5474 0.1207 -0.6548 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8000 2.3420 0.3413 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5562 1.8728 0.5321 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1298 -0.4617 -2.1035 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1764 1.2414 -2.3572 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9649 1.8900 -0.5407 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1319 0.7171 -1.6803 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9367 -0.4976 2.3599 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5009 1.1861 1.8667 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2088 -0.3199 1.2185 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0383 -1.7695 1.3413 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1081 -3.1842 0.0920 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1667 -1.8073 -0.1660 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9595 -2.3725 -1.4512 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2721 -1.8149 -1.3952 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2813 -2.9343 -0.0452 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3363 -1.4615 1.4766 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2679 1.8220 2.5956 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5959 0.1896 3.7191 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0515 -0.5511 2.5027 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7782 1.0643 2.7649 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0542 1.8861 0.6338 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3642 2.7295 3.3003 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9309 0.3851 -0.4134 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6873 1.0489 0.9331 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9257 1.4632 -0.7771 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3160 2.7017 0.4434 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6976 -0.1790 -1.2826 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8238 0.0558 -3.5228 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2249 -0.5016 -4.2225 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0722 -1.3877 -2.8532 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2837 -2.6645 0.2251 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9023 -3.2117 1.1970 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7372 -1.6072 1.5413 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 3 4 2 0 3 5 1 0 5 6 1 0 7 6 1 6 7 8 1 0 7 9 1 0 9 10 1 0 9 11 1 0 11 12 1 0 12 13 1 0 13 14 1 1 14 15 2 0 15 16 1 0 16 17 1 0 17 18 1 0 16 19 1 0 14 20 1 0 20 21 1 0 21 22 1 0 20 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 12 27 1 0 27 28 1 0 18 7 1 0 18 13 1 0 24 13 1 0 1 29 1 0 1 30 1 0 2 31 1 0 4 32 1 0 4 33 1 0 5 34 1 0 5 35 1 0 6 36 1 0 6 37 1 0 8 38 1 0 8 39 1 0 8 40 1 0 9 41 1 1 10 42 1 0 10 43 1 0 10 44 1 0 11 45 1 0 11 46 1 0 12 47 1 1 15 48 1 0 16 49 1 1 17 50 1 0 17 51 1 0 18 52 1 1 19 53 1 0 20 54 1 6 22 55 1 0 22 56 1 0 22 57 1 0 24 58 1 6 26 59 1 0 26 60 1 0 26 61 1 0 28 62 1 0 28 63 1 0 28 64 1 0 M END

Standard InCHIKey	KUSFVCHTPOSQLS-SWSYEKRDSA-N
Standard InCHI	InChI=1S/C23H36O5/c1-8-14(2)9-10-22(4)15(3)11-19(25-5)23-17(12-16(24)13-18(22)23)20(26-6)28-21(23)27-7/h8,12,15-16,18-21,24H,1-2,9-11,13H2,3-7H3/t15-,16+,18+,19+,20+,21-,22-,23-/m1/s1
SMILES	C=CC(=C)CC[C@]1(C)[C@H](C)C[C@@H]([C@@]23C(=C[C@@H](C[C@@H]12)O)[C@@H](OC)O[C@H]3OC)OC

Calculated Properties

Physi-Chem Properties

Molecular Weight:	392.26	Volume:	416.737 ? Van der Waals volume.
Dense:	0.941	LogP:	2.991 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.929 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.772 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	7.0	Rigid Bonds:	17.0
TPSA:	57.15 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	1.0	Rings:	3.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.527	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.851	Fsp³:	0.739
MCE-18:	80.5 ? 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:	0.484	Fluc inhibitor:	0.001 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.013 ? 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:	0.299	Promiscuous compounds:	0.201

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.157	MDCK Permeability:	-4.844
Pgp-inhibitor:	0.641	Pgp-substrate:	0.377
PAMPA:	0.307 ? 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):	0.026
20% Bioavailability (F20%):	0.872	30% Bioavailability (F30%):	0.874
50% Bioavailability (F50%):	0.995

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.019	MRP1:	0.64
Plasma Protein Binding (PPB):	75.892%	Volume Distribution (VD):	0.233
Fu:	25.31% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.996
OATP1B3 inhibitor:	0.982	BCRP inhibitor:	0.832
BSEP inhibitor:	0.748

ADMET: Metabolism

CYP1A2-inhibitor:	0.944	CYP1A2-substrate:	0.168
CYP2C19-inhibitor:	0.998	CYP2C19-substrate:	0.029
CYP2C9-inhibitor:	0.95	CYP2C9-substrate:	0.008
CYP2D6-inhibitor:	0.932	CYP2D6-substrate:	0.446
CYP3A4-inhibitor:	0.731	CYP3A4-substrate:	0.97
CYP2B6-substrate:	0.999	CYP2C8-inhibitor:	0.294
HLM stability:	0.969 ? 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):

15.013

Half-life (T1/2):

2.156

ADMET: Toxicity

hERG Blockers:	0.276	hERG Blockers (10um):	0.728
Human Hepatotoxicity (H-HT):	0.51	Drug-induced Liver Injury (DILI):	0.399
AMES Toxicity:	0.892	Rat Oral Acute Toxicity:	0.975
Maximum Recommended Daily Dose:	0.992	Skin Sensitization:	0.982
Carcinogencity:	0.591	Eye Corrosion:	0.0
Eye Irritation:	0.287	Respiratory Toxicity:	0.995
Drug-induced Neurotoxicity:	0.888	Ototoxicity:	0.657
Hematotoxicity:	0.634	Drug-induced Nephrotoxicity:	0.525
Genotoxicity:	0.944	RPMI-8226 Immunitoxicity:	0.388
A549 Cytotoxicity:	0.558	Hek293 Cytotoxicity:	0.504
BCF:	0.842 ? 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:	3.547 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.286 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.578 ? 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
NPO40063	Casearia graveolens	Species	Salicaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[26474353]
NPO40063	Casearia graveolens	Species	Salicaceae	Eukaryota	Leaves	n.a.	n.a.	PMID[31916761]

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
EC50	1

Activity Type	# Activity
Cell line	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
NPT681	Cell line	PC-12	Rattus norvegicus	EC50	=	3300.0	nM	PMID[26474353]

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 NPC481022 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	13850
0.1-0.2	33184
0.2-0.3	2686
0.3-0.4	70
0.4-0.5	39
0.5-0.6	20
0.6-0.7	6
0.7-0.8	0
0.8-0.85	0
0.85-0.9	2
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC488650
0.8889	High Similarity	NPC488651
0.8889	High Similarity	NPC488648
0.6667	Remote Similarity	NPC488221
0.6667	Remote Similarity	NPC488220
0.6667	Remote Similarity	NPC488216
0.6286	Remote Similarity	NPC486752
0.6129	Remote Similarity	NPC472189
0.6032	Remote Similarity	NPC481018
0.5946	Remote Similarity	NPC486759
0.5946	Remote Similarity	NPC488217
0.5946	Remote Similarity	NPC488218
0.5938	Remote Similarity	NPC481020
0.5781	Remote Similarity	NPC171598
0.5758	Remote Similarity	NPC472188
0.5692	Remote Similarity	NPC132395
0.5692	Remote Similarity	NPC471364
0.5606	Remote Similarity	NPC471362
0.5606	Remote Similarity	NPC471372
0.5606	Remote Similarity	NPC318917
0.5606	Remote Similarity	NPC481019
0.5522	Remote Similarity	NPC472186
0.5441	Remote Similarity	NPC471366
0.5441	Remote Similarity	NPC476800
0.5441	Remote Similarity	NPC488649
0.5441	Remote Similarity	NPC488237
0.5362	Remote Similarity	NPC471365
0.5362	Remote Similarity	NPC481017
0.5139	Remote Similarity	NPC472187

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC481022 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6550
0.1-0.2	2582
0.2-0.3	18
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