NPASS Compound

Natural Product: NPC115624

Natural Product ID	NPC115624
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	4-Demethyl-Deoxypodophyllotoxin-4-O-Beta-D-Glucopyranoside
IUPAC Name	(5R,5aR,8aR)-5-[3,5-dimethoxy-4-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyphenyl]-5a,8,8a,9-tetrahydro-5H-[2]benzofuro[5,6-f][1,3]benzodioxol-6-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1778163
PubChem CID	12311205
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0001392] Lignans, neolignans and related compounds [CHEMONTID:0001511] Lignan glycosides

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 74 0 0 0 0 0 0 0 0999 V2000 0.5188 2.5621 -2.0424 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2795 1.4664 -1.5765 O 0 0 0 0 0 0 0 0 0 0 0 0 0.6294 0.3533 -1.1056 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7565 0.2951 -1.0833 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4018 -0.8265 -0.6081 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6504 -1.8766 -0.1631 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7578 -1.8217 -0.1837 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3999 -0.7000 -0.6576 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7600 -0.5984 -0.6978 O 0 0 0 0 0 0 0 0 0 0 0 0 3.5930 -0.0987 0.3094 C 0 0 1 0 0 0 0 0 0 0 0 0 4.6309 -1.1614 0.6241 C 0 0 1 0 0 0 0 0 0 0 0 0 5.9601 -0.8221 -0.0348 C 0 0 2 0 0 0 0 0 0 0 0 0 6.4786 0.5137 0.4149 C 0 0 1 0 0 0 0 0 0 0 0 0 5.2940 1.4228 0.6588 C 0 0 1 0 0 0 0 0 0 0 0 0 5.6677 2.8607 0.3111 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5873 3.7053 0.4384 O 0 0 0 0 0 0 0 0 0 0 0 0 4.2754 0.9983 -0.2173 O 0 0 0 0 0 0 0 0 0 0 0 0 7.2777 0.4044 1.5650 O 0 0 0 0 0 0 0 0 0 0 0 0 5.6994 -0.7446 -1.4170 O 0 0 0 0 0 0 0 0 0 0 0 0 4.7836 -1.3129 1.9987 O 0 0 0 0 0 0 0 0 0 0 0 0 1.5150 -2.8879 0.2694 O 0 0 0 0 0 0 0 0 0 0 0 0 0.9938 -4.0776 0.7724 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8491 -0.8858 -0.6191 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.5778 0.3335 -0.1812 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9917 1.4054 0.4671 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7922 2.4924 0.7490 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1243 2.5152 0.4016 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7146 1.4161 -0.2577 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9200 0.3489 -0.5308 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4896 -0.9230 -1.1443 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0934 -1.8814 -0.1212 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.4439 -3.2974 -0.0852 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4592 -3.7600 0.9006 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.4780 -2.7280 1.0584 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7880 -2.4807 2.0408 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.5494 -2.0876 -0.2430 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.6798 3.7274 0.8046 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.6403 4.5069 1.3405 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4868 3.6870 1.3771 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.1947 2.9055 -1.2461 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1525 2.2146 -2.8801 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1302 3.3890 -2.4233 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2619 1.1781 -1.4725 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0278 -2.8178 0.2056 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0683 0.2360 1.2068 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3236 -2.1381 0.2178 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6677 -1.6304 0.1953 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0697 0.9870 -0.4221 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8879 1.3517 1.6746 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5072 3.1680 0.9643 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0156 2.8312 -0.7578 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8519 4.4783 1.0205 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7759 0.8354 2.2942 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5924 -1.6723 -1.7993 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9831 -0.9292 2.4280 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5445 -3.9808 1.7768 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2779 -4.4878 0.0362 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8412 -4.8117 0.8275 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0498 -0.8136 -1.7872 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9437 1.3680 0.7489 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7606 1.4276 -0.5331 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5868 -0.7978 -1.2855 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9599 -1.0626 -2.0960 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2082 -1.4114 0.9083 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2672 -3.7837 -1.0479 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4614 -3.4487 0.3248 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5110 -2.8916 -1.0763 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4438 5.3704 0.6642 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9229 4.8939 2.3341 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 2 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 14 17 1 0 13 18 1 0 12 19 1 0 11 20 1 0 7 21 1 0 21 22 1 0 5 23 1 0 23 24 1 0 24 25 2 0 25 26 1 0 26 27 2 0 27 28 1 0 28 29 2 0 29 30 1 0 30 31 1 0 31 32 1 0 32 33 1 0 33 34 1 0 34 35 2 0 34 36 1 0 27 37 1 0 37 38 1 0 38 39 1 0 8 3 1 0 17 10 1 0 36 23 1 0 29 24 1 0 36 31 1 0 39 26 1 0 1 40 1 0 1 41 1 0 1 42 1 0 4 43 1 0 6 44 1 0 10 45 1 1 11 46 1 6 12 47 1 6 13 48 1 6 14 49 1 1 15 50 1 0 15 51 1 0 16 52 1 0 18 53 1 0 19 54 1 0 20 55 1 0 22 56 1 0 22 57 1 0 22 58 1 0 23 59 1 6 25 60 1 0 28 61 1 0 30 62 1 0 30 63 1 0 31 64 1 1 32 65 1 0 32 66 1 0 36 67 1 6 38 68 1 0 38 69 1 0 M END

Standard InCHIKey	QMXNRLBPHJPLKV-QNRBAVQLSA-N
Standard InCHI	InChI=1S/C27H30O12/c1-33-17-5-12(6-18(34-2)25(17)39-27-24(31)23(30)22(29)19(8-28)38-27)20-14-7-16-15(36-10-37-16)4-11(14)3-13-9-35-26(32)21(13)20/h4-7,13,19-24,27-31H,3,8-10H2,1-2H3/t13-,19+,20+,21-,22+,23-,24+,27-/m0/s1
SMILES	COc1cc(cc(c1O[C@H]1[C@@H]([C@H]([C@@H]([C@@H](CO)O1)O)O)O)OC)[C@@H]1c2cc3c(cc2C[C@H]2COC(=O)[C@H]12)OCO3

Calculated Properties

Physi-Chem Properties

Molecular Weight:	546.17	Volume:	511.237 ? Van der Waals volume.
Dense:	1.068	LogP:	0.667 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.172 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.426 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	Rigid Bonds:	32.0
TPSA:	162.6 ? Topological Polar Surface Area.	H-Bond Acceptor:	12.0
H-Bond Donor:	4.0	Rings:	6.0
Heavy Atoms:	12.0

MedChem Properties

QED Drug-Likeness Score:	0.362	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.492	Fsp³:	0.519
MCE-18:	123.78 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.735	Fluc inhibitor:	0.011 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.202 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.086 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.041	Promiscuous compounds:	0.246

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.794	MDCK Permeability:	-5.042
Pgp-inhibitor:	0.0	Pgp-substrate:	0.003
PAMPA:	0.863 ? 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%):	0.005	30% Bioavailability (F30%):	0.0
50% Bioavailability (F50%):	0.22

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.996	MRP1:	0.565
Plasma Protein Binding (PPB):	94.813%	Volume Distribution (VD):	-0.302
Fu:	5.531% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.965
OATP1B3 inhibitor:	0.921	BCRP inhibitor:	0.0
BSEP inhibitor:	0.089

ADMET: Metabolism

CYP1A2-inhibitor:	0.003	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.001
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.313
CYP3A4-inhibitor:	0.898	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.008
HLM stability:	0.072 ? 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):

2.5

Half-life (T1/2):

3.662

ADMET: Toxicity

hERG Blockers:	0.068	hERG Blockers (10um):	0.169
Human Hepatotoxicity (H-HT):	0.964	Drug-induced Liver Injury (DILI):	0.999
AMES Toxicity:	0.971	Rat Oral Acute Toxicity:	0.329
Maximum Recommended Daily Dose:	0.286	Skin Sensitization:	1.0
Carcinogencity:	0.731	Eye Corrosion:	0.0
Eye Irritation:	0.003	Respiratory Toxicity:	0.258
Drug-induced Neurotoxicity:	0.514	Ototoxicity:	0.989
Hematotoxicity:	0.962	Drug-induced Nephrotoxicity:	0.997
Genotoxicity:	0.998	RPMI-8226 Immunitoxicity:	0.724
A549 Cytotoxicity:	0.937	Hek293 Cytotoxicity:	0.796
BCF:	0.745 ? 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:	3.444 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.152 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.223 ? 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
NPO14752	Sinopodophyllum emodi	Species	Berberidaceae	Eukaryota	roots and rhizomes	n.a.	n.a.	PMID[21570846]
NPO14752	Sinopodophyllum emodi	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO14752	Sinopodophyllum emodi	Species	Berberidaceae	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	2

Activity Type	# Activity
Cell line	2

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
NPT165	Cell line	HeLa	Homo sapiens	IC50	=	870.0	nM	PMID[12444683]
NPT91	Cell line	KB	Homo sapiens	IC50	=	2090.0	nM	PMID[11170665]

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 NPC115624 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	18423
0.1-0.2	27725
0.2-0.3	3107
0.3-0.4	493
0.4-0.5	86
0.5-0.6	12
0.6-0.7	10
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
0.7778	Intermediate Similarity	NPC222531
0.6806	Remote Similarity	NPC80230
0.6806	Remote Similarity	NPC104024
0.6806	Remote Similarity	NPC101755
0.6806	Remote Similarity	NPC304687
0.6806	Remote Similarity	NPC65574
0.6712	Remote Similarity	NPC262455
0.6712	Remote Similarity	NPC177476
0.6026	Remote Similarity	NPC30009
0.6026	Remote Similarity	NPC103197
0.6023	Remote Similarity	NPC152424
0.5789	Remote Similarity	NPC218092
0.5789	Remote Similarity	NPC246474
0.5789	Remote Similarity	NPC162851
0.5579	Remote Similarity	NPC306475
0.5375	Remote Similarity	NPC149505
0.5375	Remote Similarity	NPC480477
0.5319	Remote Similarity	NPC116759
0.5319	Remote Similarity	NPC14294
0.5238	Remote Similarity	NPC115281
0.5233	Remote Similarity	NPC158635
0.5233	Remote Similarity	NPC229882
0.5106	Remote Similarity	NPC486547

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC115624 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5265
0.1-0.2	3787
0.2-0.3	80
0.3-0.4	12
0.4-0.5	6
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