NPASS Compound

Natural Product: NPC554755

Natural Product ID	NPC554755
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(2~{R},3~{R},4~{S},5~{R},6~{S})-2-(hydroxymethyl)-6-[[4-[(2~{S},3~{R},4~{S},5~{R},6~{R})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-1-naphthyl]oxy]tetrahydropyran-3,4,5-triol
IUPAC Name	(2~{R},3~{R},4~{S},5~{R},6~{S})-2-(hydroxymethyl)-6-[[4-[(2~{S},3~{R},4~{S},5~{R},6~{R})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-1-naphthyl]oxy]tetrahydropyran-3,4,5-triol
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 62 65 0 0 0 0 0 0 0 0999 V2000 4.7644 -0.7650 -2.2119 O 0 0 0 0 0 0 0 0 0 0 0 0 5.4562 -0.4427 -1.0317 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5383 1.0439 -0.8864 C 0 0 1 0 0 0 0 0 0 0 0 0 4.3332 1.6936 -0.8199 O 0 0 0 0 0 0 0 0 0 0 0 0 3.5624 1.3788 0.3013 C 0 0 1 0 0 0 0 0 0 0 0 0 2.8463 0.1987 0.1520 O 0 0 0 0 0 0 0 0 0 0 0 0 1.4828 0.0100 0.1230 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5947 1.0298 0.2381 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7902 0.7993 0.2041 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2999 -0.4616 0.0531 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6191 -0.7013 0.0176 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.7222 0.1263 0.1099 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.5895 -0.1292 1.1074 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.9128 -0.1978 0.9046 C 0 0 2 0 0 0 0 0 0 0 0 0 -6.3632 -1.6468 0.8494 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0714 -2.3117 2.0488 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.4977 0.5973 -0.2131 C 0 0 2 0 0 0 0 0 0 0 0 0 -7.2563 -0.2747 -1.0050 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.4695 1.2227 -1.1204 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.9858 1.6209 -2.3280 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.3745 0.1781 -1.2768 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.4244 0.5767 -2.2170 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.3991 -1.4980 -0.0640 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8343 -2.8029 -0.2186 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0443 -3.8585 -0.3367 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3805 -3.6140 -0.3006 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8587 -2.3262 -0.1479 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9634 -1.2873 -0.0319 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4264 1.3498 1.5510 C 0 0 2 0 0 0 0 0 0 0 0 0 3.7673 1.9067 2.6511 O 0 0 0 0 0 0 0 0 0 0 0 0 5.7267 2.0762 1.3730 C 0 0 1 0 0 0 0 0 0 0 0 0 6.4400 1.9580 2.5579 O 0 0 0 0 0 0 0 0 0 0 0 0 6.4800 1.3755 0.2541 C 0 0 1 0 0 0 0 0 0 0 0 0 7.0090 0.2060 0.8251 O 0 0 0 0 0 0 0 0 0 0 0 0 5.0979 -1.6038 -2.6170 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9939 -0.9618 -0.1918 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5048 -0.8262 -1.0997 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0480 1.4325 -1.8136 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8747 2.2345 0.4355 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9247 2.0495 0.3591 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4064 1.6815 0.3045 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3489 1.1849 0.2653 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4028 0.2071 1.8469 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8785 -2.2233 0.0533 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4827 -1.7189 0.7276 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6659 -3.1213 2.1253 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1916 1.3977 0.1164 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1372 -0.0795 -1.9649 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0133 2.0629 -0.5486 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6553 2.3289 -2.1428 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8640 -0.7703 -1.5478 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8792 1.2870 -2.7654 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8927 -3.0465 -0.2529 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3011 -4.8921 -0.4591 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1048 -4.4277 -0.3916 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9053 -2.1191 -0.1175 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6560 0.2980 1.8192 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1694 2.6440 2.4058 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5892 3.1572 1.1727 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9222 1.0798 2.6174 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3137 2.0274 -0.0386 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9502 0.0587 0.5905 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 2 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 17 18 1 0 17 19 1 0 19 20 1 0 19 21 1 0 21 22 1 0 10 23 1 0 23 24 2 0 24 25 1 0 25 26 2 0 26 27 1 0 27 28 2 0 5 29 1 0 29 30 1 0 29 31 1 0 31 32 1 0 31 33 1 0 33 34 1 0 33 3 1 0 28 7 1 0 21 12 1 0 28 23 1 0 1 35 1 0 2 36 1 0 2 37 1 0 3 38 1 6 5 39 1 1 8 40 1 0 9 41 1 0 12 42 1 1 14 43 1 1 15 44 1 0 15 45 1 0 16 46 1 0 17 47 1 1 18 48 1 0 19 49 1 1 20 50 1 0 21 51 1 6 22 52 1 0 24 53 1 0 25 54 1 0 26 55 1 0 27 56 1 0 29 57 1 1 30 58 1 0 31 59 1 6 32 60 1 0 33 61 1 6 34 62 1 0 M END

Standard InCHIKey	JZCXWLYHHFCGQT-XCCNGPICSA-N
Standard InCHI	InChI=1S/C22H28O12/c23-7-13-15(25)17(27)19(29)21(33-13)31-11-5-6-12(10-4-2-1-3-9(10)11)32-22-20(30)18(28)16(26)14(8-24)34-22/h1-6,13-30H,7-8H2/t13-,14-,15+,16+,17+,18+,19-,20-,21-,22-/m1/s1
SMILES	OC[C@H]1O[C@@H](OC2=CC=C(O[C@@H]3O[C@H](CO)[C@H](O)[C@H](O)[C@H]3O)C3=CC=CC=C23)[C@H](O)[C@@H](O)[C@H]1O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	484.16	Volume:	447.143 ? Van der Waals volume.
Dense:	1.083	LogP:	0.08 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	0.855 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-1.717 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	Rigid Bonds:	23.0
TPSA:	198.76 ? Topological Polar Surface Area.	H-Bond Acceptor:	12.0
H-Bond Donor:	8.0	Rings:	4.0
Heavy Atoms:	12.0

MedChem Properties

QED Drug-Likeness Score:	0.21	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.189	Fsp³:	0.545
MCE-18:	93.294 ? 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:	Rejected	BMS Rule:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.48	Fluc inhibitor:	0.002 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.188 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.023 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.467	Promiscuous compounds:	0.038

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.765	MDCK Permeability:	-5.012
Pgp-inhibitor:	0.0	Pgp-substrate:	0.658
PAMPA:	1.0 ? 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):	0.981
20% Bioavailability (F20%):	0.831	30% Bioavailability (F30%):	0.999
50% Bioavailability (F50%):	0.995

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.005	MRP1:	0.1
Plasma Protein Binding (PPB):	72.673%	Volume Distribution (VD):	-0.376
Fu:	29.032% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.979
OATP1B3 inhibitor:	0.981	BCRP inhibitor:	0.001
BSEP inhibitor:	0.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.029
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.054
HLM stability:	0.109 ? 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):

1.203

Half-life (T1/2):

3.043

ADMET: Toxicity

hERG Blockers:	0.013	hERG Blockers (10um):	0.063
Human Hepatotoxicity (H-HT):	0.787	Drug-induced Liver Injury (DILI):	0.844
AMES Toxicity:	0.97	Rat Oral Acute Toxicity:	0.01
Maximum Recommended Daily Dose:	0.002	Skin Sensitization:	0.999
Carcinogencity:	0.084	Eye Corrosion:	0.0
Eye Irritation:	0.02	Respiratory Toxicity:	0.002
Drug-induced Neurotoxicity:	0.007	Ototoxicity:	0.995
Hematotoxicity:	0.572	Drug-induced Nephrotoxicity:	0.936
Genotoxicity:	0.045	RPMI-8226 Immunitoxicity:	0.175
A549 Cytotoxicity:	0.621	Hek293 Cytotoxicity:	0.166
BCF:	0.775 ? 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:	3.119 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.433 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.69 ? 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
NPO16607	Rubia yunnanensis	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[12350148]
NPO16607	Rubia yunnanensis	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[12762798]
NPO16607	Rubia yunnanensis	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[21044847]
NPO16607	Rubia yunnanensis	Species	Rubiaceae	Eukaryota	n.a.	root	n.a.	PMID[21973054]
NPO16607	Rubia yunnanensis	Species	Rubiaceae	Eukaryota	roots	n.a.	n.a.	PMID[21973054]
NPO16607	Rubia yunnanensis	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO16607	Rubia yunnanensis	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO16607	Rubia yunnanensis	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO16607	Rubia yunnanensis	Species	Rubiaceae	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 NPC554755 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	19349
0.1-0.2	27425
0.2-0.3	2178
0.3-0.4	631
0.4-0.5	229
0.5-0.6	39
0.6-0.7	2
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
0.6744	Remote Similarity	NPC228907
0.6226	Remote Similarity	NPC485268
0.5833	Remote Similarity	NPC212729
0.5833	Remote Similarity	NPC142319
0.5833	Remote Similarity	NPC604498
0.58	Remote Similarity	NPC9248
0.5714	Remote Similarity	NPC269242
0.56	Remote Similarity	NPC153149
0.56	Remote Similarity	NPC294470
0.5577	Remote Similarity	NPC226712
0.5577	Remote Similarity	NPC608788
0.551	Remote Similarity	NPC276195
0.55	Remote Similarity	NPC604276
0.55	Remote Similarity	NPC605751
0.55	Remote Similarity	NPC611254
0.55	Remote Similarity	NPC611275
0.549	Remote Similarity	NPC25817
0.5439	Remote Similarity	NPC288349
0.541	Remote Similarity	NPC216752
0.54	Remote Similarity	NPC217854
0.54	Remote Similarity	NPC484157
0.5397	Remote Similarity	NPC17432
0.5385	Remote Similarity	NPC60589
0.5385	Remote Similarity	NPC469708
0.5385	Remote Similarity	NPC604439
0.5385	Remote Similarity	NPC609376
0.5294	Remote Similarity	NPC192810
0.5283	Remote Similarity	NPC200092
0.5192	Remote Similarity	NPC152722
0.5185	Remote Similarity	NPC221090
0.5185	Remote Similarity	NPC80098
0.5167	Remote Similarity	NPC600105
0.5156	Remote Similarity	NPC478798
0.5094	Remote Similarity	NPC299144
0.5091	Remote Similarity	NPC166168
0.5091	Remote Similarity	NPC214454
0.5091	Remote Similarity	NPC166040
0.5077	Remote Similarity	NPC600548
0.5077	Remote Similarity	NPC603192
0.5077	Remote Similarity	NPC606398
0.5077	Remote Similarity	NPC610995

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC554755 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5019
0.1-0.2	3985
0.2-0.3	121
0.3-0.4	21
0.4-0.5	3
0.5-0.6	1
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
0.5577	Remote Similarity	NPD1091	Pre-clinical

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