NPASS Compound

Natural Product: NPC2049

Natural Product ID	NPC2049
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Jaspiferoic Acid B Dimethyl Ester
IUPAC Name	methyl (3E,3aS,5aR,6R,7R,9aR,9bR)-7-acetyloxy-3-[(E)-5-methoxy-5-oxopent-3-en-2-ylidene]-3a,6,9a-trimethyl-2-oxo-1,4,5,5a,7,8,9,9b-octahydrocyclopenta[a]naphthalene-6-carboxylate
Synonyms	Jaspiferoic Acid B Dimethyl Ester
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL496068
PubChem CID	44583730
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001549] Monoterpenoids

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 69 71 0 0 0 0 0 0 0 0999 V2000 4.5310 -3.0251 0.1702 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6477 -1.8258 0.0730 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4551 -1.8426 0.6945 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9614 -2.9705 1.4674 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6065 -3.9434 1.9497 O 0 0 0 0 0 0 0 0 0 0 0 0 0.4963 -2.7904 1.6094 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3540 -1.2977 1.5885 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.0109 -0.7658 1.3895 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.9549 -1.9746 1.4975 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4804 0.1859 2.4854 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8795 1.5314 1.9595 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9090 1.4729 0.8594 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.5052 0.4777 -0.2388 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.3375 1.2550 -1.5687 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1725 -0.0307 0.1054 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.4705 -0.8335 -0.9466 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0229 -0.5752 -0.7248 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4560 -0.7731 0.7113 C 0 0 2 0 0 0 0 0 0 0 0 0 2.0441 0.4875 1.3256 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5781 -0.4665 -0.5049 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6772 -0.3593 0.0790 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.4217 -1.5004 -1.4001 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.5095 -2.3789 -1.6059 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9603 2.7597 0.2751 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.0734 3.5551 0.2030 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1403 3.1209 0.6901 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.9493 4.8821 -0.4473 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0311 -0.6638 -0.6532 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1740 -0.5080 -1.3459 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4463 0.7425 -2.0499 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5189 0.8445 -2.6836 O 0 0 0 0 0 0 0 0 0 0 0 0 4.5793 1.8215 -2.0518 O 0 0 0 0 0 0 0 0 0 0 0 0 4.8697 3.0299 -2.7439 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6868 -3.3571 1.2231 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5175 -2.8592 -0.2453 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0492 -3.8325 -0.4572 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0058 -3.3528 0.8345 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2287 -3.2332 2.6042 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6504 -0.9763 2.6381 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9786 -1.6288 1.7470 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9436 -2.6168 0.6258 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6343 -2.5131 2.4402 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3028 -0.2299 3.1010 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6320 0.3328 3.1822 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0293 2.2058 1.7270 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4048 2.0431 2.8222 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8933 1.1731 1.2624 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3288 1.6840 -1.5885 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1547 1.9763 -1.6939 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4583 0.5117 -2.3872 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5536 0.9177 0.2212 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6632 -1.9004 -0.9368 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7078 -0.4329 -1.9431 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1230 0.5273 -0.9466 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6104 -1.1213 -1.4628 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0792 0.2782 1.6246 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5414 0.7400 2.2875 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8580 1.3268 0.6694 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3666 -3.2920 -0.9537 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4396 -1.9162 -1.2769 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5716 -2.7019 -2.6665 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1790 4.7363 -1.5371 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8984 5.2355 -0.4221 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5787 5.6495 -0.0008 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4048 0.2044 -0.6960 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8760 -1.3219 -1.3709 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8960 3.3406 -2.4076 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8277 2.9291 -3.8321 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2000 3.8330 -2.3536 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 3 4 1 0 4 5 2 0 4 6 1 0 6 7 1 0 7 8 1 0 8 9 1 6 8 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 6 13 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 1 1 13 20 1 0 20 21 2 0 20 22 1 0 22 23 1 0 12 24 1 0 24 25 1 0 25 26 2 0 25 27 1 0 2 28 1 0 28 29 2 0 29 30 1 0 30 31 2 0 30 32 1 0 32 33 1 0 18 3 1 0 18 7 1 0 15 8 1 0 1 34 1 0 1 35 1 0 1 36 1 0 6 37 1 0 6 38 1 0 7 39 1 1 9 40 1 0 9 41 1 0 9 42 1 0 10 43 1 0 10 44 1 0 11 45 1 0 11 46 1 0 12 47 1 1 14 48 1 0 14 49 1 0 14 50 1 0 15 51 1 1 16 52 1 0 16 53 1 0 17 54 1 0 17 55 1 0 19 56 1 0 19 57 1 0 19 58 1 0 23 59 1 0 23 60 1 0 23 61 1 0 27 62 1 0 27 63 1 0 27 64 1 0 28 65 1 0 29 66 1 0 33 67 1 0 33 68 1 0 33 69 1 0 M END

Standard InCHIKey	LLEIOSQDYZKAKA-DRMGVFQJSA-N
Standard InCHI	InChI=1S/C26H36O7/c1-15(8-9-21(29)31-6)22-17(28)14-19-24(3)13-11-20(33-16(2)27)26(5,23(30)32-7)18(24)10-12-25(19,22)4/h8-9,18-20H,10-14H2,1-7H3/b9-8+,22-15-/t18-,19-,20-,24+,25+,26-/m1/s1
SMILES	C/C(=C/1C(=O)C[C@@H]2[C@@]3(C)CC[C@H]([C@@](C)([C@@H]3CC[C@]12C)C(=O)OC)OC(=O)C)/C=C/C(=O)OC

Calculated Properties

Physi-Chem Properties

Molecular Weight:	460.25	Volume:	478.296 ? Van der Waals volume.
Dense:	0.962	LogP:	2.759 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.867 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.258 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	7.0	Rigid Bonds:	21.0
TPSA:	95.97 ? Topological Polar Surface Area.	H-Bond Acceptor:	7.0
H-Bond Donor:	0.0	Rings:	3.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.356	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.582	Fsp³:	0.692
MCE-18:	67.5 ? 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:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.272	Fluc inhibitor:	0.107 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.101 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.007 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.583	Promiscuous compounds:	0.567

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.996	MDCK Permeability:	-4.823
Pgp-inhibitor:	0.995	Pgp-substrate:	0.018
PAMPA:	0.019 ? 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):	0.002
20% Bioavailability (F20%):	0.133	30% Bioavailability (F30%):	0.372
50% Bioavailability (F50%):	0.922

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.005	MRP1:	0.994
Plasma Protein Binding (PPB):	91.485%	Volume Distribution (VD):	-0.086
Fu:	7.478% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.999	BCRP inhibitor:	0.088
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.288	CYP1A2-substrate:	0.766
CYP2C19-inhibitor:	0.533	CYP2C19-substrate:	0.26
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.015
CYP2D6-inhibitor:	0.005	CYP2D6-substrate:	0.02
CYP3A4-inhibitor:	0.171	CYP3A4-substrate:	0.126
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.999
HLM stability:	0.983 ? 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):

7.858

Half-life (T1/2):

0.565

ADMET: Toxicity

hERG Blockers:	0.027	hERG Blockers (10um):	0.16
Human Hepatotoxicity (H-HT):	0.702	Drug-induced Liver Injury (DILI):	0.886
AMES Toxicity:	0.496	Rat Oral Acute Toxicity:	0.485
Maximum Recommended Daily Dose:	0.717	Skin Sensitization:	0.991
Carcinogencity:	0.797	Eye Corrosion:	0.056
Eye Irritation:	0.569	Respiratory Toxicity:	0.408
Drug-induced Neurotoxicity:	0.185	Ototoxicity:	0.241
Hematotoxicity:	0.653	Drug-induced Nephrotoxicity:	0.812
Genotoxicity:	0.965	RPMI-8226 Immunitoxicity:	0.071
A549 Cytotoxicity:	0.221	Hek293 Cytotoxicity:	0.324
BCF:	0.763 ? 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:	3.69 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.342 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.845 ? 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
NPO33335	Jaspis sp.	Species	Ancorinidae	Eukaryota	n.a.	Vanuatu islands	n.a.	PMID[10924170]
NPO33335	Jaspis sp.	Species	Ancorinidae	Eukaryota	n.a.	n.a.	n.a.	PMID[11277766]
NPO33335	Jaspis sp.	Species	Ancorinidae	Eukaryota	n.a.	depth of 25 m off the shore of Keomun Island, Korea	2004-AUG	PMID[18407691]
NPO33335	Jaspis sp.	Species	Ancorinidae	Eukaryota	n.a.	n.a.	n.a.	PMID[18990572]
NPO33335	Jaspis sp.	Species	Ancorinidae	Eukaryota	n.a.	n.a.	n.a.	PMID[8326327]
NPO33335	Jaspis sp.	Species	Ancorinidae	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
IC50	1

Activity Type	# Activity
Non-molecular	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
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	>	3.3	ug.mL-1	PMID[10924170]

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 NPC2049 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	17497
0.1-0.2	26660
0.2-0.3	5435
0.3-0.4	213
0.4-0.5	28
0.5-0.6	13
0.6-0.7	4
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
0.7759	Intermediate Similarity	NPC151725
0.75	Intermediate Similarity	NPC473435
0.75	Intermediate Similarity	NPC473280
0.75	Intermediate Similarity	NPC471078
0.7273	Intermediate Similarity	NPC161638
0.7273	Intermediate Similarity	NPC80335
0.7258	Intermediate Similarity	NPC106425
0.7258	Intermediate Similarity	NPC122324
0.6923	Remote Similarity	NPC473482
0.6923	Remote Similarity	NPC473284
0.6818	Remote Similarity	NPC473283
0.6818	Remote Similarity	NPC475526
0.5606	Remote Similarity	NPC474842
0.5606	Remote Similarity	NPC475965
0.5606	Remote Similarity	NPC604299
0.5507	Remote Similarity	NPC6206
0.5507	Remote Similarity	NPC469874
0.5429	Remote Similarity	NPC10064
0.5429	Remote Similarity	NPC266955
0.5429	Remote Similarity	NPC170221
0.5352	Remote Similarity	NPC155332
0.5352	Remote Similarity	NPC114540
0.5286	Remote Similarity	NPC605871
0.5278	Remote Similarity	NPC115899
0.5211	Remote Similarity	NPC110937

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC2049 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6425
0.1-0.2	2616
0.2-0.3	108
0.3-0.4	1
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