NPASS Compound

Natural Product: NPC551105

Natural Product ID	NPC551105
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Dihydrosyringetin
IUPAC Name	(2~{R},3~{R})-3,5,7-trihydroxy-2-(4-hydroxy-3,5-dimethoxy-phenyl)chroman-4-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds]

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 41 43 0 0 0 0 0 0 0 0999 V2000 -3.1532 -3.7560 -0.2651 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8575 -2.4997 -0.2055 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.3746 -1.2937 -0.2887 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2185 -0.9835 -1.0345 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7008 0.2792 -1.1308 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5223 0.5958 -1.9117 C 0 0 1 0 0 0 0 0 0 0 0 0 1.3904 1.4531 -1.1741 O 0 0 0 0 0 0 0 0 0 0 0 0 2.0762 0.9638 -0.0508 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4875 1.8022 0.9650 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1672 1.3079 2.0766 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5766 2.1774 3.0987 O 0 0 0 0 0 0 0 0 0 0 0 0 3.4083 -0.0459 2.1157 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9974 -0.8817 1.1028 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2242 -2.2586 1.1091 O 0 0 0 0 0 0 0 0 0 0 0 0 2.3152 -0.3925 -0.0156 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8805 -1.2743 -1.0865 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0329 -2.5105 -0.9353 O 0 0 0 0 0 0 0 0 0 0 0 0 1.2801 -0.6711 -2.3028 C 0 0 2 0 0 0 0 0 0 0 0 0 2.3644 -0.2103 -3.0894 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.3761 1.2728 -0.4475 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5079 1.0058 0.2905 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1589 2.0553 0.9685 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.6418 3.3733 0.8703 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0295 -0.2536 0.3908 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1783 -0.5334 1.1386 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.7740 -4.0327 -1.1783 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7798 -4.1755 0.5815 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2389 -4.4213 -0.2531 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7583 -1.8183 -1.5335 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2843 1.1239 -2.8541 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2816 2.8823 0.9094 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5181 2.5994 3.0635 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9323 -0.4489 2.9692 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8035 -2.7506 1.7433 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6558 -1.3306 -2.8939 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0741 0.1799 -2.5126 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9604 2.2668 -0.5295 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1891 4.0028 1.6039 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5609 3.4139 1.0632 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7869 3.7935 -0.1590 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0271 -0.0060 1.0487 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 1 0 6 7 1 0 7 8 1 0 8 9 2 0 9 10 1 0 10 11 1 0 10 12 2 0 12 13 1 0 13 14 1 0 13 15 2 0 15 16 1 0 16 17 2 0 16 18 1 0 18 19 1 0 5 20 2 0 20 21 1 0 21 22 1 0 22 23 1 0 21 24 2 0 24 25 1 0 24 3 1 0 18 6 1 0 15 8 1 0 1 26 1 0 1 27 1 0 1 28 1 0 4 29 1 0 6 30 1 6 9 31 1 0 11 32 1 0 12 33 1 0 14 34 1 0 18 35 1 6 19 36 1 0 20 37 1 0 23 38 1 0 23 39 1 0 23 40 1 0 25 41 1 0 M END

Standard InCHIKey	OGGVSBOPKJAJQA-DLBZAZTESA-N
Standard InCHI	InChI=1S/C17H16O8/c1-23-11-3-7(4-12(24-2)14(11)20)17-16(22)15(21)13-9(19)5-8(18)6-10(13)25-17/h3-6,16-20,22H,1-2H3/t16-,17+/m0/s1
SMILES	COC1=CC([C@H]2OC3=CC(O)=CC(O)=C3C(=O)[C@@H]2O)=CC(OC)=C1O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	348.08	Volume:	328.785 ? Van der Waals volume.
Dense:	1.059	LogP:	1.021 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.388 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.48 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	18.0
TPSA:	125.68 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	4.0	Rings:	3.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.657	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.321	Fsp³:	0.235
MCE-18:	63.81 ? 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:	1
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.491	Fluc inhibitor:	0.316 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.109 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.333 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.33	Promiscuous compounds:	0.297

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.901	MDCK Permeability:	-5.177
Pgp-inhibitor:	0.914	Pgp-substrate:	0.388
PAMPA:	0.044 ? 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):	0.066
20% Bioavailability (F20%):	0.018	30% Bioavailability (F30%):	0.813
50% Bioavailability (F50%):	0.997

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.001	MRP1:	0.911
Plasma Protein Binding (PPB):	96.75%	Volume Distribution (VD):	-0.202
Fu:	2.862% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.989
BSEP inhibitor:	0.588

ADMET: Metabolism

CYP1A2-inhibitor:	0.012	CYP1A2-substrate:	0.029
CYP2C19-inhibitor:	0.03	CYP2C19-substrate:	0.317
CYP2C9-inhibitor:	0.03	CYP2C9-substrate:	0.009
CYP2D6-inhibitor:	0.501	CYP2D6-substrate:	0.82
CYP3A4-inhibitor:	0.081	CYP3A4-substrate:	0.136
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.956
HLM stability:	0.976 ? 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):

7.283

Half-life (T1/2):

2.1

ADMET: Toxicity

hERG Blockers:	0.092	hERG Blockers (10um):	0.484
Human Hepatotoxicity (H-HT):	0.81	Drug-induced Liver Injury (DILI):	0.736
AMES Toxicity:	0.634	Rat Oral Acute Toxicity:	0.659
Maximum Recommended Daily Dose:	0.636	Skin Sensitization:	0.97
Carcinogencity:	0.448	Eye Corrosion:	0.005
Eye Irritation:	0.954	Respiratory Toxicity:	0.794
Drug-induced Neurotoxicity:	0.471	Ototoxicity:	0.342
Hematotoxicity:	0.455	Drug-induced Nephrotoxicity:	0.74
Genotoxicity:	0.915	RPMI-8226 Immunitoxicity:	0.307
A549 Cytotoxicity:	0.836	Hek293 Cytotoxicity:	0.736
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:	3.363 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.465 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.822 ? 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
NPO120	Tecoma stans	Species	Bignoniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO120	Tecoma stans	Species	Bignoniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO120	Tecoma stans	Species	Bignoniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO120	Tecoma stans	Species	Bignoniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO120	Tecoma stans	Species	Bignoniaceae	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

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

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 NPC551105 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	26123
0.1-0.2	19369
0.2-0.3	3848
0.3-0.4	386
0.4-0.5	85
0.5-0.6	16
0.6-0.7	17
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
0.7736	Intermediate Similarity	NPC326037
0.7736	Intermediate Similarity	NPC13858
0.7451	Intermediate Similarity	NPC44721
0.7451	Intermediate Similarity	NPC211466
0.7451	Intermediate Similarity	NPC605332
0.7358	Intermediate Similarity	NPC320825
0.7308	Intermediate Similarity	NPC250922
0.72	Intermediate Similarity	NPC21835
0.7059	Intermediate Similarity	NPC62290
0.7059	Intermediate Similarity	NPC142731
0.7059	Intermediate Similarity	NPC326506
0.7059	Intermediate Similarity	NPC4152
0.6923	Remote Similarity	NPC19721
0.6667	Remote Similarity	NPC36835
0.6667	Remote Similarity	NPC246162
0.6667	Remote Similarity	NPC9743
0.6667	Remote Similarity	NPC260491
0.6667	Remote Similarity	NPC61506
0.6667	Remote Similarity	NPC240476
0.6415	Remote Similarity	NPC279417
0.6415	Remote Similarity	NPC208176
0.6415	Remote Similarity	NPC49130
0.6182	Remote Similarity	NPC306607
0.6182	Remote Similarity	NPC606962
0.6029	Remote Similarity	NPC36916
0.6029	Remote Similarity	NPC36
0.6029	Remote Similarity	NPC7154
0.6029	Remote Similarity	NPC125039
0.6029	Remote Similarity	NPC7688
0.597	Remote Similarity	NPC606364
0.5942	Remote Similarity	NPC138688
0.5942	Remote Similarity	NPC72787
0.5942	Remote Similarity	NPC217795
0.5942	Remote Similarity	NPC58223
0.5857	Remote Similarity	NPC279209
0.5857	Remote Similarity	NPC102277
0.5857	Remote Similarity	NPC479117
0.5614	Remote Similarity	NPC176869
0.5614	Remote Similarity	NPC3779
0.5593	Remote Similarity	NPC52530
0.5439	Remote Similarity	NPC122828
0.5172	Remote Similarity	NPC201837
0.5088	Remote Similarity	NPC476182
0.5085	Remote Similarity	NPC263449
0.5085	Remote Similarity	NPC308992

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC551105 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5581
0.1-0.2	3492
0.2-0.3	67
0.3-0.4	2
0.4-0.5	5
0.5-0.6	0
0.6-0.7	3
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
0.6029	Remote Similarity	NPD6166	Phase 2
0.6029	Remote Similarity	NPD6167	Clinical (unspecified phase)
0.6029	Remote Similarity	NPD6168	Clinical (unspecified phase)

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