NPASS Compound

Natural Product: NPC476748

Natural Product ID	NPC476748
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	1,4-Butanediol, 2,3-bis(1,3-benzodioxol-5-ylmethyl)-, diacetate, (2R,3R)-
IUPAC Name	[(2R,3R)-3-(acetyloxymethyl)-4-(1,3-benzodioxol-5-yl)-2-(1,3-benzodioxol-5-ylmethyl)butyl] acetate
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	5488712
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0001392] Lignans, neolignans and related compounds [CHEMONTID:0001969] Dibenzylbutane lignans

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 58 61 0 0 0 0 0 0 0 0999 V2000 -2.0871 1.0605 4.5804 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3392 1.2670 3.1332 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4434 1.7962 2.8090 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.4223 0.9053 2.1583 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.7617 1.1455 0.8163 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6417 0.6895 -0.1497 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.4834 -0.8024 0.0646 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7305 -1.5487 -0.2414 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0118 -1.9747 -1.5476 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1509 -2.6822 -1.8660 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0478 -2.9834 -0.8664 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7860 -2.5679 0.4433 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6303 -1.8558 0.7390 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0792 -3.6864 -1.4599 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.0500 -3.5072 -2.8627 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6615 -3.2138 -3.0571 O 0 0 0 0 0 0 0 0 0 0 0 0 0.5367 1.5267 0.0950 C 0 0 1 0 0 0 0 0 0 0 0 0 1.7676 1.4400 -0.6785 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5007 0.1603 -0.7092 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4989 -0.7382 -1.7555 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2199 -1.9105 -1.6811 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9726 -2.2507 -0.5779 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9869 -1.3741 0.4679 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2692 -0.1989 0.4035 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5583 -3.4864 -0.8464 O 0 0 0 0 0 0 0 0 0 0 0 0 4.4429 -3.7540 -2.2243 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3537 -2.9466 -2.6172 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0949 2.9174 0.5023 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0494 3.8702 0.7320 O 0 0 0 0 0 0 0 0 0 0 0 0 1.8823 4.5781 -0.0511 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8445 4.4202 -1.2907 O 0 0 0 0 0 0 0 0 0 0 0 0 2.8840 5.5748 0.4802 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6397 2.0158 4.9834 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0615 0.8336 5.0688 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3945 0.2165 4.7211 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0520 2.1877 0.6773 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7037 0.5706 0.5426 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0426 0.8436 -1.1635 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3684 -1.2850 -0.3460 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3595 -0.8929 1.1960 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2921 -1.7251 -2.3112 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5007 -2.8121 1.2194 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4562 -1.5563 1.7565 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3812 -4.3775 -3.4300 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6625 -2.5834 -3.0712 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8890 1.1208 1.1739 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5117 2.1459 -0.1794 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6835 1.8552 -1.7240 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9141 -0.4791 -2.6187 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5813 -1.6467 1.3344 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3310 0.4469 1.2760 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2060 -4.8181 -2.3659 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3572 -3.4877 -2.7955 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6591 3.2783 -0.2652 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4913 2.8605 1.4846 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3255 6.4863 0.7515 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3389 5.1438 1.4184 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6545 5.7882 -0.2755 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 9 10 1 0 10 11 2 0 11 12 1 0 12 13 2 0 11 14 1 0 14 15 1 0 15 16 1 0 6 17 1 0 17 18 1 0 18 19 1 0 19 20 2 0 20 21 1 0 21 22 2 0 22 23 1 0 23 24 2 0 22 25 1 0 25 26 1 0 26 27 1 0 17 28 1 0 28 29 1 0 29 30 1 0 30 31 2 0 30 32 1 0 13 8 1 0 16 10 1 0 24 19 1 0 27 21 1 0 1 33 1 0 1 34 1 0 1 35 1 0 5 36 1 0 5 37 1 0 6 38 1 6 7 39 1 0 7 40 1 0 9 41 1 0 12 42 1 0 13 43 1 0 15 44 1 0 15 45 1 0 17 46 1 1 18 47 1 0 18 48 1 0 20 49 1 0 23 50 1 0 24 51 1 0 26 52 1 0 26 53 1 0 28 54 1 0 28 55 1 0 32 56 1 0 32 57 1 0 32 58 1 0 M END

Standard InCHIKey	GFOPJZZAXNTRGJ-PMACEKPBSA-N
Standard InCHI	InChI=1S/C24H26O8/c1-15(25)27-11-19(7-17-3-5-21-23(9-17)31-13-29-21)20(12-28-16(2)26)8-18-4-6-22-24(10-18)32-14-30-22/h3-6,9-10,19-20H,7-8,11-14H2,1-2H3/t19-,20-/m0/s1
SMILES	CC(=O)OC[C@H](CC1=CC2=C(C=C1)OCO2)[C@@H](CC3=CC4=C(C=C3)OCO4)COC(=O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	442.16	Volume:	438.664 ? Van der Waals volume.
Dense:	1.008	LogP:	2.516 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.631 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.303 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	11.0	Rigid Bonds:	22.0
TPSA:	89.52 ? 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:	0.547	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.376	Fsp³:	0.417
MCE-18:	68.588 ? 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:	0.374	Fluc inhibitor:	0.311 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.018 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.343 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.322	Promiscuous compounds:	0.174

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.742	MDCK Permeability:	-4.637
Pgp-inhibitor:	0.989	Pgp-substrate:	0.009
PAMPA:	0.038 ? 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):	0.0
20% Bioavailability (F20%):	0.039	30% Bioavailability (F30%):	0.001
50% Bioavailability (F50%):	0.668

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.386	MRP1:	0.748
Plasma Protein Binding (PPB):	97.066%	Volume Distribution (VD):	-0.252
Fu:	4.189% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.992
OATP1B3 inhibitor:	0.812	BCRP inhibitor:	0.018
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.486	CYP1A2-substrate:	0.995
CYP2C19-inhibitor:	0.999	CYP2C19-substrate:	0.797
CYP2C9-inhibitor:	0.872	CYP2C9-substrate:	1.0
CYP2D6-inhibitor:	0.977	CYP2D6-substrate:	1.0
CYP3A4-inhibitor:	0.867	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.949	CYP2C8-inhibitor:	0.013
HLM stability:	0.93 ? 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):

1.764

Half-life (T1/2):

0.99

ADMET: Toxicity

hERG Blockers:	0.406	hERG Blockers (10um):	0.271
Human Hepatotoxicity (H-HT):	0.898	Drug-induced Liver Injury (DILI):	0.783
AMES Toxicity:	0.805	Rat Oral Acute Toxicity:	0.151
Maximum Recommended Daily Dose:	0.651	Skin Sensitization:	0.572
Carcinogencity:	0.422	Eye Corrosion:	0.001
Eye Irritation:	0.788	Respiratory Toxicity:	0.14
Drug-induced Neurotoxicity:	0.816	Ototoxicity:	0.5
Hematotoxicity:	0.37	Drug-induced Nephrotoxicity:	0.768
Genotoxicity:	0.955	RPMI-8226 Immunitoxicity:	0.13
A549 Cytotoxicity:	0.099	Hek293 Cytotoxicity:	0.201
BCF:	1.024 ? 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:	4.003 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.506 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.122 ? 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
NPO3925	Bursera microphylla	Species	Burseraceae	Eukaryota	Resin	Baha de Kino	2013-JAN	PMID[25966052]
NPO3925	Bursera microphylla	Species	Burseraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO3925	Bursera microphylla	Species	Burseraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO3925	Bursera microphylla	Species	Burseraceae	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	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
NPT113	Cell line	RAW264.7	Mus musculus	IC50	=	9800	nM	PMID[25966052]

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 NPC476748 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	18739
0.1-0.2	28645
0.2-0.3	1932
0.3-0.4	364
0.4-0.5	114
0.5-0.6	31
0.6-0.7	20
0.7-0.8	0
0.8-0.85	1
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8605	High Similarity	NPC143895
0.8	Intermediate Similarity	NPC600801
0.7727	Intermediate Similarity	NPC110958
0.7727	Intermediate Similarity	NPC19890
0.7273	Intermediate Similarity	NPC11453
0.7083	Intermediate Similarity	NPC205915
0.6957	Remote Similarity	NPC192255
0.68	Remote Similarity	NPC176586
0.68	Remote Similarity	NPC210354
0.675	Remote Similarity	NPC80241
0.675	Remote Similarity	NPC301641
0.675	Remote Similarity	NPC485483
0.6667	Remote Similarity	NPC158737
0.6667	Remote Similarity	NPC487679
0.6667	Remote Similarity	NPC191158
0.6667	Remote Similarity	NPC487678
0.6667	Remote Similarity	NPC177644
0.6458	Remote Similarity	NPC171550
0.6458	Remote Similarity	NPC134764
0.6182	Remote Similarity	NPC145569
0.6154	Remote Similarity	NPC18576
0.6136	Remote Similarity	NPC344161
0.6071	Remote Similarity	NPC56184
0.6038	Remote Similarity	NPC47181
0.6038	Remote Similarity	NPC230968
0.6038	Remote Similarity	NPC102260
0.5965	Remote Similarity	NPC282291
0.5965	Remote Similarity	NPC166137
0.5926	Remote Similarity	NPC3982
0.5909	Remote Similarity	NPC40352
0.5909	Remote Similarity	NPC213711
0.5882	Remote Similarity	NPC165128
0.5814	Remote Similarity	NPC81067
0.5814	Remote Similarity	NPC602945
0.5741	Remote Similarity	NPC185908
0.5741	Remote Similarity	NPC482891
0.5625	Remote Similarity	NPC223807
0.56	Remote Similarity	NPC474288
0.551	Remote Similarity	NPC249788
0.551	Remote Similarity	NPC485482
0.549	Remote Similarity	NPC92693
0.5476	Remote Similarity	NPC31279
0.5385	Remote Similarity	NPC40237
0.5294	Remote Similarity	NPC104077
0.5294	Remote Similarity	NPC219671
0.5294	Remote Similarity	NPC147616
0.5294	Remote Similarity	NPC485480
0.52	Remote Similarity	NPC196937
0.52	Remote Similarity	NPC606623
0.5192	Remote Similarity	NPC211386
0.5167	Remote Similarity	NPC169973
0.5161	Remote Similarity	NPC156376
0.5094	Remote Similarity	NPC274356
0.5094	Remote Similarity	NPC101748
0.5088	Remote Similarity	NPC218092
0.5088	Remote Similarity	NPC246474
0.5088	Remote Similarity	NPC162851

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC476748 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3564
0.1-0.2	5290
0.2-0.3	277
0.3-0.4	16
0.4-0.5	1
0.5-0.6	2
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
0.5217	Remote Similarity	NPD554	Phase 3
0.5156	Remote Similarity	NPD5563	Phase 2

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