NPASS Compound

Natural Product: NPC488648

Natural Product ID	NPC488648
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	LAISVTGBXQDEAU-LUBGZTNYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	127034478
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 66 68 0 0 0 0 0 0 0 0999 V2000 5.3954 0.6604 -0.8748 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5263 -0.5865 -0.5119 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6662 -1.3537 0.3519 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9740 -2.6075 0.6262 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4519 -0.7398 0.9468 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3703 -0.5503 -0.0582 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1243 0.0685 0.5445 C 0 0 2 0 0 0 0 0 0 0 0 0 1.5388 1.4182 1.1129 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5897 -0.7426 1.6643 C 0 0 2 0 0 0 0 0 0 0 0 0 0.7036 -2.2363 1.5370 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7920 -0.4305 2.0874 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5053 0.6429 1.2957 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.2839 0.5116 -0.1761 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.0053 1.5492 -0.9691 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3946 2.4748 -1.6527 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0564 2.6515 -1.7601 C 0 0 1 0 0 0 0 0 0 0 0 0 0.7667 1.4181 -1.3953 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1361 0.3636 -0.5831 C 0 0 1 0 0 0 0 0 0 0 0 0 0.4389 3.1535 -3.0192 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.4260 1.2218 -0.7969 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.1282 1.2002 -2.0144 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.1789 2.0894 -2.0332 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4706 -0.0759 -0.2842 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.1993 -0.6280 -0.6370 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.0167 -1.8502 -0.0614 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.9079 -2.9743 -0.8933 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9815 -2.8069 -2.1599 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.7144 -4.3483 -0.4188 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8308 0.4987 1.7022 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.2665 1.5344 2.5163 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6176 1.3446 -0.5909 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1430 1.0957 -1.5439 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3991 -1.1228 -0.9121 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8613 -3.0492 0.2055 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3170 -3.1614 1.2757 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8115 0.2897 1.2690 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1656 -1.2141 1.8975 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1158 -1.5103 -0.5913 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7600 0.0822 -0.8650 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8865 2.2449 0.8384 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5591 1.7301 0.8348 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5347 1.3877 2.2313 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2833 -0.4919 2.5404 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9045 -2.6280 0.5491 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2752 -2.7376 1.8394 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4184 -2.6954 2.2643 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4507 -1.3209 2.1045 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7938 -0.0649 3.1428 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2079 1.6482 1.7227 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0515 3.1868 -2.1980 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3322 3.4752 -1.0683 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7670 1.7764 -0.9717 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1001 0.9485 -2.3866 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1656 -0.6067 -1.1953 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0142 2.5374 -3.6845 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9506 1.9763 -0.2014 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6671 2.0065 -3.0181 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8903 3.1285 -1.7671 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9554 1.7660 -1.2886 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2301 -0.6979 -1.7379 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0524 -4.8814 -1.1637 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3114 -4.4647 0.5834 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7044 -4.8819 -0.5417 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6390 1.5863 3.4555 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2874 1.2768 2.8630 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3259 2.5155 2.0231 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 6 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 26 27 2 0 26 28 1 0 12 29 1 0 29 30 1 0 18 7 1 0 18 13 1 0 24 13 1 0 1 31 1 0 1 32 1 0 2 33 1 0 4 34 1 0 4 35 1 0 5 36 1 0 5 37 1 0 6 38 1 0 6 39 1 0 8 40 1 0 8 41 1 0 8 42 1 0 9 43 1 1 10 44 1 0 10 45 1 0 10 46 1 0 11 47 1 0 11 48 1 0 12 49 1 1 15 50 1 0 16 51 1 1 17 52 1 0 17 53 1 0 18 54 1 6 19 55 1 0 20 56 1 1 22 57 1 0 22 58 1 0 22 59 1 0 24 60 1 6 28 61 1 0 28 62 1 0 28 63 1 0 30 64 1 0 30 65 1 0 30 66 1 0 M END

Standard InCHIKey	LAISVTGBXQDEAU-LUBGZTNYSA-N
Standard InCHI	InChI=1S/C24H36O6/c1-8-14(2)9-10-23(5)15(3)11-20(27-6)24-18(12-17(26)13-19(23)24)21(28-7)30-22(24)29-16(4)25/h8,12,15,17,19-22,26H,1-2,9-11,13H2,3-7H3/t15-,17+,19+,20+,21+,22+,23-,24-/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(=O)C)OC

Calculated Properties

Physi-Chem Properties

Molecular Weight:	420.25	Volume:	440.186 ? Van der Waals volume.
Dense:	0.955	LogP:	3.086 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.956 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.884 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	8.0	Rigid Bonds:	18.0
TPSA:	74.22 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	1.0	Rings:	3.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.384	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.785	Fsp³:	0.708
MCE-18:	83.707 ? 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:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.506	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.012 ? 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:	0.257	Promiscuous compounds:	0.607

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.279	MDCK Permeability:	-4.942
Pgp-inhibitor:	0.721	Pgp-substrate:	0.22
PAMPA:	0.364 ? 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):	0.023
20% Bioavailability (F20%):	0.92	30% Bioavailability (F30%):	0.964
50% Bioavailability (F50%):	0.997

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.095	MRP1:	0.9
Plasma Protein Binding (PPB):	69.26%	Volume Distribution (VD):	0.039
Fu:	29.8% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.997
OATP1B3 inhibitor:	0.983	BCRP inhibitor:	0.758
BSEP inhibitor:	0.602

ADMET: Metabolism

CYP1A2-inhibitor:	0.003	CYP1A2-substrate:	0.082
CYP2C19-inhibitor:	0.981	CYP2C19-substrate:	0.007
CYP2C9-inhibitor:	0.293	CYP2C9-substrate:	0.023
CYP2D6-inhibitor:	0.008	CYP2D6-substrate:	0.055
CYP3A4-inhibitor:	0.009	CYP3A4-substrate:	0.797
CYP2B6-substrate:	0.422	CYP2C8-inhibitor:	0.973
HLM stability:	0.968 ? 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):

12.381

Half-life (T1/2):

1.595

ADMET: Toxicity

hERG Blockers:	0.148	hERG Blockers (10um):	0.554
Human Hepatotoxicity (H-HT):	0.546	Drug-induced Liver Injury (DILI):	0.743
AMES Toxicity:	0.922	Rat Oral Acute Toxicity:	0.959
Maximum Recommended Daily Dose:	0.986	Skin Sensitization:	0.995
Carcinogencity:	0.764	Eye Corrosion:	0.0
Eye Irritation:	0.13	Respiratory Toxicity:	0.975
Drug-induced Neurotoxicity:	0.862	Ototoxicity:	0.556
Hematotoxicity:	0.735	Drug-induced Nephrotoxicity:	0.685
Genotoxicity:	0.936	RPMI-8226 Immunitoxicity:	0.354
A549 Cytotoxicity:	0.806	Hek293 Cytotoxicity:	0.533
BCF:	0.639 ? 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:	3.458 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.265 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.503 ? 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
NPO32459	casearia balansae	Species	Salicaceae	Eukaryota	leaves and twigs	n.a.	n.a.	PMID[24033131]
NPO32459	casearia balansae	Species	Salicaceae	Eukaryota	twigs	n.a.	n.a.	PMID[25286284]
NPO32459	casearia balansae	Species	Salicaceae	Eukaryota	Leaves	n.a.	n.a.	PMID[26699618]
NPO32459	casearia balansae	Species	Salicaceae	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

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	=	2900.0	nM	PMID[26699618]

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 NPC488648 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	13760
0.1-0.2	30933
0.2-0.3	5003
0.3-0.4	64
0.4-0.5	49
0.5-0.6	17
0.6-0.7	20
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	NPC488651
0.8889	High Similarity	NPC488650
0.8889	High Similarity	NPC481022
0.7538	Intermediate Similarity	NPC488221
0.7538	Intermediate Similarity	NPC488220
0.7538	Intermediate Similarity	NPC488216
0.7101	Intermediate Similarity	NPC486752
0.7049	Intermediate Similarity	NPC472189
0.6935	Remote Similarity	NPC481018
0.6825	Remote Similarity	NPC481020
0.6712	Remote Similarity	NPC486759
0.6712	Remote Similarity	NPC488217
0.6712	Remote Similarity	NPC488218
0.6667	Remote Similarity	NPC171598
0.6615	Remote Similarity	NPC472188
0.6562	Remote Similarity	NPC132395
0.6562	Remote Similarity	NPC471364
0.6462	Remote Similarity	NPC471362
0.6462	Remote Similarity	NPC471372
0.6462	Remote Similarity	NPC318917
0.6462	Remote Similarity	NPC481019
0.6364	Remote Similarity	NPC472186
0.6269	Remote Similarity	NPC471366
0.6269	Remote Similarity	NPC476800
0.6269	Remote Similarity	NPC488649
0.6269	Remote Similarity	NPC488237
0.6176	Remote Similarity	NPC471365
0.6176	Remote Similarity	NPC481017
0.5915	Remote Similarity	NPC472187
0.5652	Remote Similarity	NPC488236
0.5526	Remote Similarity	NPC486753
0.5429	Remote Similarity	NPC479943
0.5417	Remote Similarity	NPC473545
0.5417	Remote Similarity	NPC238397
0.5316	Remote Similarity	NPC230331
0.5316	Remote Similarity	NPC267469
0.5316	Remote Similarity	NPC470024
0.5301	Remote Similarity	NPC486754
0.5278	Remote Similarity	NPC479940
0.5278	Remote Similarity	NPC7644
0.527	Remote Similarity	NPC488219
0.525	Remote Similarity	NPC17791
0.525	Remote Similarity	NPC328074
0.5135	Remote Similarity	NPC48548
0.5125	Remote Similarity	NPC321272

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC488648 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6088
0.1-0.2	3005
0.2-0.3	57
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