NPASS Compound

Natural Product: NPC539691

Natural Product ID	NPC539691
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	3-[(2~{S},3~{R},4~{R},5~{S},6~{R})-6-[[(2~{R},3~{R},4~{S},5~{S},6~{S})-3,5-dihydroxy-6-methyl-4-[(2~{S},3~{R},4~{S},5~{R},6~{R})-3,4,5-trihydroxy-6-methyl-tetrahydropyran-2-yl]oxy-tetrahydropyran-2-yl]oxymethyl]-3,4,5-trihydroxy-tetrahydropyran-2-yl]oxy-5-hydroxy-2-(4-hydroxyphenyl)-7-methoxy-chromen-4-one
IUPAC Name	3-[(2~{S},3~{R},4~{R},5~{S},6~{R})-6-[[(2~{R},3~{R},4~{S},5~{S},6~{S})-3,5-dihydroxy-6-methyl-4-[(2~{S},3~{R},4~{S},5~{R},6~{R})-3,4,5-trihydroxy-6-methyl-tetrahydropyran-2-yl]oxy-tetrahydropyran-2-yl]oxymethyl]-3,4,5-trihydroxy-tetrahydropyran-2-yl]oxy-5-hydroxy-2-(4-hydroxyphenyl)-7-methoxy-chromen-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 95100 0 0 0 0 0 0 0 0999 V2000 11.7111 0.4655 1.5210 C 0 0 0 0 0 0 0 0 0 0 0 0 10.8183 0.6533 2.6008 O 0 0 0 0 0 0 0 0 0 0 0 0 9.4539 0.5359 2.3281 C 0 0 0 0 0 0 0 0 0 0 0 0 8.5410 0.7139 3.3664 C 0 0 0 0 0 0 0 0 0 0 0 0 7.1935 0.6009 3.1122 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2826 0.7759 4.1377 O 0 0 0 0 0 0 0 0 0 0 0 0 6.7276 0.3119 1.8362 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3919 0.1906 1.5581 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5873 0.3522 2.5018 O 0 0 0 0 0 0 0 0 0 0 0 0 4.9078 -0.1087 0.2481 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6399 -0.2065 0.1226 O 0 0 0 0 0 0 0 0 0 0 0 0 2.3462 -0.3062 -0.0055 C 0 0 2 0 0 0 0 0 0 0 0 0 1.6095 -0.3634 1.2093 O 0 0 0 0 0 0 0 0 0 0 0 0 0.2457 -0.1885 0.8084 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.4887 0.4406 1.9386 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7838 0.7309 1.7327 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.1339 1.5980 0.7438 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.4734 2.8730 1.2831 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.4929 2.8136 2.1921 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.9050 4.2612 2.4741 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6865 2.0520 1.7345 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.9027 1.0266 2.6841 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.6282 1.5219 0.3461 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.3347 0.2935 0.3612 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.4621 0.3275 -0.4514 C 0 0 2 0 0 0 0 0 0 0 0 0 -7.5424 0.0568 0.3912 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.7614 0.1424 -0.2611 C 0 0 2 0 0 0 0 0 0 0 0 0 -9.8379 -0.2099 0.7462 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.8724 -0.8525 -1.3959 C 0 0 2 0 0 0 0 0 0 0 0 0 -9.1306 -2.1241 -0.9360 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.6194 -0.8894 -2.2348 C 0 0 2 0 0 0 0 0 0 0 0 0 -7.6032 -2.1635 -2.8505 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.3600 -0.7839 -1.4390 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.2963 -0.6102 -2.3277 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.2355 1.1988 -0.1564 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.1058 1.9409 -1.3625 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.2296 -1.5924 0.4602 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.1055 -1.4706 -0.6271 O 0 0 0 0 0 0 0 0 0 0 0 0 0.9939 -2.3997 0.0342 C 0 0 1 0 0 0 0 0 0 0 0 0 0.5921 -3.4607 -0.7705 O 0 0 0 0 0 0 0 0 0 0 0 0 1.9143 -1.5260 -0.8114 C 0 0 1 0 0 0 0 0 0 0 0 0 1.2879 -1.1768 -2.0023 O 0 0 0 0 0 0 0 0 0 0 0 0 5.8612 -0.2629 -0.7126 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6028 -0.5718 -2.1318 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4341 -0.3473 -2.7622 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2458 -0.7484 -4.1002 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2324 -1.3785 -4.8196 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0647 -1.7803 -6.1371 O 0 0 0 0 0 0 0 0 0 0 0 0 6.4223 -1.5988 -4.1613 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6223 -1.2162 -2.8606 C 0 0 0 0 0 0 0 0 0 0 0 0 7.1588 -0.1364 -0.3889 O 0 0 0 0 0 0 0 0 0 0 0 0 7.6081 0.1318 0.7934 C 0 0 0 0 0 0 0 0 0 0 0 0 8.9501 0.2539 1.0920 C 0 0 0 0 0 0 0 0 0 0 0 0 12.7646 0.4442 1.8362 H 0 0 0 0 0 0 0 0 0 0 0 0 11.5285 1.3035 0.7917 H 0 0 0 0 0 0 0 0 0 0 0 0 11.5058 -0.4925 0.9921 H 0 0 0 0 0 0 0 0 0 0 0 0 8.9532 0.9362 4.3367 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0143 -0.0349 4.7117 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8889 0.5915 -0.5159 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2313 0.3992 -0.1237 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1307 1.3068 2.2897 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4450 -0.3015 2.7993 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2239 1.8616 0.1316 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0577 2.4307 3.1569 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1678 4.3487 3.5449 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0904 4.9627 2.1997 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7944 4.5464 1.8724 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6184 2.6869 1.8225 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6453 0.1527 2.2702 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1936 2.1976 -0.3314 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5620 1.3003 -0.9550 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.9834 1.1320 -0.6689 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.7021 -1.2993 0.9869 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.7286 0.3288 1.6873 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.8401 -0.1389 0.2891 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.7028 -0.5417 -2.0684 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.0844 -2.3380 -1.0730 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.6913 -0.1484 -3.0645 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.6099 -2.8722 -2.1661 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2528 -1.7362 -0.8632 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2359 -1.3615 -2.9450 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1690 0.1449 -0.4903 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2107 2.8979 -1.1224 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6912 -2.1131 1.3034 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3658 -2.3437 -0.9906 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5435 -2.7809 0.8951 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2396 -4.1925 -0.8204 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7938 -2.1444 -1.0657 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1643 -1.9909 -2.5186 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6493 0.1837 -2.2564 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2867 -0.5419 -4.5497 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4419 -1.1852 -6.8822 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2290 -2.1026 -4.7131 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5687 -1.4040 -2.3717 H 0 0 0 0 0 0 0 0 0 0 0 0 9.6773 0.1178 0.2905 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 5 7 2 0 7 8 1 0 8 9 2 0 8 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 16 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 19 21 1 0 21 22 1 0 21 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 26 27 1 0 27 28 1 0 27 29 1 0 29 30 1 0 29 31 1 0 31 32 1 0 31 33 1 0 33 34 1 0 23 35 1 0 35 36 1 0 14 37 1 0 37 38 1 0 37 39 1 0 39 40 1 0 39 41 1 0 41 42 1 0 10 43 2 0 43 44 1 0 44 45 2 0 45 46 1 0 46 47 2 0 47 48 1 0 47 49 1 0 49 50 2 0 43 51 1 0 51 52 1 0 52 53 2 0 53 3 1 0 52 7 1 0 41 12 1 0 50 44 1 0 35 17 1 0 33 25 1 0 1 54 1 0 1 55 1 0 1 56 1 0 4 57 1 0 6 58 1 0 12 59 1 6 14 60 1 6 15 61 1 0 15 62 1 0 17 63 1 6 19 64 1 1 20 65 1 0 20 66 1 0 20 67 1 0 21 68 1 6 22 69 1 0 23 70 1 6 25 71 1 6 27 72 1 6 28 73 1 0 28 74 1 0 28 75 1 0 29 76 1 6 30 77 1 0 31 78 1 6 32 79 1 0 33 80 1 1 34 81 1 0 35 82 1 6 36 83 1 0 37 84 1 1 38 85 1 0 39 86 1 1 40 87 1 0 41 88 1 6 42 89 1 0 45 90 1 0 46 91 1 0 48 92 1 0 49 93 1 0 50 94 1 0 53 95 1 0 M END

Standard InCHIKey	MQMTVWHXCSRCER-HUTZIQEMSA-N
Standard InCHI	InChI=1S/C34H42O19/c1-11-20(37)24(41)26(43)33(49-11)52-30-21(38)12(2)48-32(28(30)45)47-10-18-22(39)25(42)27(44)34(51-18)53-31-23(40)19-16(36)8-15(46-3)9-17(19)50-29(31)13-4-6-14(35)7-5-13/h4-9,11-12,18,20-22,24-28,30,32-39,41-45H,10H2,1-3H3/t11-,12+,18-,20+,21+,22-,24+,25-,26-,27-,28-,30+,32-,33+,34+/m1/s1
SMILES	COC1=CC(O)=C2C(=O)C(O[C@@H]3O[C@H](CO[C@@H]4O[C@@H](C)[C@H](O)[C@H](O[C@@H]5O[C@H](C)[C@H](O)[C@H](O)[C@H]5O)[C@H]4O)[C@@H](O)[C@@H](O)[C@H]3O)=C(C3=CC=C(O)C=C3)OC2=C1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	754.23	Volume:	691.204 ? Van der Waals volume.
Dense:	1.091	LogP:	0.955 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.539 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.152 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	9.0	Rigid Bonds:	36.0
TPSA:	297.12 ? Topological Polar Surface Area.	H-Bond Acceptor:	19.0
H-Bond Donor:	10.0	Rings:	6.0
Heavy Atoms:	19.0

MedChem Properties

QED Drug-Likeness Score:	0.11	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.296	Fsp³:	0.559
MCE-18:	149.774 ? 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:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.613	Fluc inhibitor:	0.309 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.666 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.469 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.122	Promiscuous compounds:	0.423

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.529	MDCK Permeability:	-5.183
Pgp-inhibitor:	0.0	Pgp-substrate:	0.959
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):	0.364
20% Bioavailability (F20%):	0.057	30% Bioavailability (F30%):	0.92
50% Bioavailability (F50%):	0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.05
Plasma Protein Binding (PPB):	80.848%	Volume Distribution (VD):	-0.113
Fu:	17.177% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.998
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.494
BSEP inhibitor:	0.015

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:	0.001
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.202
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.997
HLM stability:	0.774 ? 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):

0.86

Half-life (T1/2):

4.338

ADMET: Toxicity

hERG Blockers:	0.017	hERG Blockers (10um):	0.122
Human Hepatotoxicity (H-HT):	0.348	Drug-induced Liver Injury (DILI):	0.927
AMES Toxicity:	0.964	Rat Oral Acute Toxicity:	0.011
Maximum Recommended Daily Dose:	0.019	Skin Sensitization:	0.999
Carcinogencity:	0.035	Eye Corrosion:	0.0
Eye Irritation:	0.047	Respiratory Toxicity:	0.009
Drug-induced Neurotoxicity:	0.002	Ototoxicity:	0.979
Hematotoxicity:	0.244	Drug-induced Nephrotoxicity:	0.317
Genotoxicity:	0.47	RPMI-8226 Immunitoxicity:	0.175
A549 Cytotoxicity:	0.858	Hek293 Cytotoxicity:	0.843
BCF:	0.421 ? 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:	3.144 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.737 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.845 ? 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
NPO27803	Cercidiphyllum japonicum	Species	Cercidiphyllaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO51667	Rhamnus thymifolius	Genus	Rhamnaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO51330	Rhamnus leptophylla	Species	Rhamnaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO54783	Rhamnus nepalensis	Genus	Rhamnaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO27803	Cercidiphyllum japonicum	Species	Cercidiphyllaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO27803	Cercidiphyllum japonicum	Species	Cercidiphyllaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO27803	Cercidiphyllum japonicum	Species	Cercidiphyllaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO27803	Cercidiphyllum japonicum	Species	Cercidiphyllaceae	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 NPC539691 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	22107
0.1-0.2	23991
0.2-0.3	2882
0.3-0.4	416
0.4-0.5	275
0.5-0.6	116
0.6-0.7	51
0.7-0.8	1
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8315	Intermediate Similarity	NPC186816
0.7653	Intermediate Similarity	NPC189564
0.7471	Intermediate Similarity	NPC46420
0.7396	Intermediate Similarity	NPC142142
0.7128	Intermediate Similarity	NPC173582
0.7128	Intermediate Similarity	NPC265885
0.7128	Intermediate Similarity	NPC181465
0.7128	Intermediate Similarity	NPC215710
0.7128	Intermediate Similarity	NPC473438
0.7128	Intermediate Similarity	NPC253788
0.7059	Intermediate Similarity	NPC292019
0.7059	Intermediate Similarity	NPC202908
0.7045	Intermediate Similarity	NPC249281
0.699	Remote Similarity	NPC25523
0.6979	Remote Similarity	NPC473571
0.6979	Remote Similarity	NPC110941
0.69	Remote Similarity	NPC101636
0.6882	Remote Similarity	NPC276377
0.6863	Remote Similarity	NPC203145
0.6771	Remote Similarity	NPC44931
0.6703	Remote Similarity	NPC271692
0.6701	Remote Similarity	NPC65563
0.6701	Remote Similarity	NPC470949
0.6667	Remote Similarity	NPC470443
0.6596	Remote Similarity	NPC116458
0.6596	Remote Similarity	NPC246943
0.6566	Remote Similarity	NPC240306
0.6538	Remote Similarity	NPC121703
0.6531	Remote Similarity	NPC203259
0.6531	Remote Similarity	NPC33054
0.6531	Remote Similarity	NPC176740
0.6531	Remote Similarity	NPC471725
0.6531	Remote Similarity	NPC134532
0.6531	Remote Similarity	NPC150164
0.6531	Remote Similarity	NPC602582
0.6471	Remote Similarity	NPC476472
0.6471	Remote Similarity	NPC294815
0.6471	Remote Similarity	NPC16194
0.6436	Remote Similarity	NPC32641
0.6436	Remote Similarity	NPC256188
0.6429	Remote Similarity	NPC67105
0.64	Remote Similarity	NPC126784
0.64	Remote Similarity	NPC241423
0.6364	Remote Similarity	NPC210073
0.6355	Remote Similarity	NPC480441
0.6327	Remote Similarity	NPC471079
0.6275	Remote Similarity	NPC72016
0.6275	Remote Similarity	NPC35119
0.6275	Remote Similarity	NPC473327
0.6275	Remote Similarity	NPC606657
0.6237	Remote Similarity	NPC297987
0.6237	Remote Similarity	NPC158674
0.62	Remote Similarity	NPC22062
0.62	Remote Similarity	NPC473634
0.62	Remote Similarity	NPC138811
0.6195	Remote Similarity	NPC209550
0.6154	Remote Similarity	NPC473073
0.6117	Remote Similarity	NPC209296
0.61	Remote Similarity	NPC39834
0.6095	Remote Similarity	NPC470449
0.6042	Remote Similarity	NPC611303
0.6019	Remote Similarity	NPC12013
0.6019	Remote Similarity	NPC11432
0.6019	Remote Similarity	NPC477613
0.5981	Remote Similarity	NPC470455
0.5941	Remote Similarity	NPC227508
0.5918	Remote Similarity	NPC605784
0.5913	Remote Similarity	NPC138990
0.5905	Remote Similarity	NPC486577
0.5882	Remote Similarity	NPC303913
0.5862	Remote Similarity	NPC175429
0.5851	Remote Similarity	NPC111929
0.5851	Remote Similarity	NPC320283
0.5851	Remote Similarity	NPC41121
0.5849	Remote Similarity	NPC470447
0.5833	Remote Similarity	NPC14187
0.5794	Remote Similarity	NPC298171
0.5784	Remote Similarity	NPC67326
0.5769	Remote Similarity	NPC488074
0.5741	Remote Similarity	NPC602448
0.5728	Remote Similarity	NPC156869
0.5714	Remote Similarity	NPC277532
0.566	Remote Similarity	NPC483416
0.5648	Remote Similarity	NPC221342
0.5648	Remote Similarity	NPC476470
0.5625	Remote Similarity	NPC108831
0.5625	Remote Similarity	NPC182634
0.5619	Remote Similarity	NPC488073
0.5619	Remote Similarity	NPC64425
0.5596	Remote Similarity	NPC470446
0.5567	Remote Similarity	NPC136042
0.5565	Remote Similarity	NPC488086
0.5521	Remote Similarity	NPC331652
0.5514	Remote Similarity	NPC122467
0.551	Remote Similarity	NPC84362
0.551	Remote Similarity	NPC27640
0.5508	Remote Similarity	NPC241781
0.5495	Remote Similarity	NPC89052
0.549	Remote Similarity	NPC116864
0.549	Remote Similarity	NPC244776
0.5472	Remote Similarity	NPC153755
0.5464	Remote Similarity	NPC289667
0.5463	Remote Similarity	NPC488089
0.5455	Remote Similarity	NPC135358
0.5437	Remote Similarity	NPC251417
0.5392	Remote Similarity	NPC476215
0.5377	Remote Similarity	NPC129264
0.5377	Remote Similarity	NPC204693
0.5364	Remote Similarity	NPC470445
0.5354	Remote Similarity	NPC24043
0.5327	Remote Similarity	NPC470125
0.5327	Remote Similarity	NPC64051
0.5317	Remote Similarity	NPC249560
0.5315	Remote Similarity	NPC470450
0.5306	Remote Similarity	NPC127546
0.5306	Remote Similarity	NPC57625
0.5306	Remote Similarity	NPC173637
0.5306	Remote Similarity	NPC317489
0.5306	Remote Similarity	NPC238376
0.5306	Remote Similarity	NPC223424
0.5306	Remote Similarity	NPC600591
0.53	Remote Similarity	NPC59534
0.5294	Remote Similarity	NPC223747
0.5283	Remote Similarity	NPC473512
0.5283	Remote Similarity	NPC129827
0.5278	Remote Similarity	NPC65711
0.5278	Remote Similarity	NPC483415
0.5273	Remote Similarity	NPC85751
0.5273	Remote Similarity	NPC19240
0.5273	Remote Similarity	NPC89127
0.5263	Remote Similarity	NPC173837
0.5248	Remote Similarity	NPC129217
0.5242	Remote Similarity	NPC473554
0.5242	Remote Similarity	NPC483159
0.5242	Remote Similarity	NPC483160
0.5238	Remote Similarity	NPC187379
0.5238	Remote Similarity	NPC609888
0.5229	Remote Similarity	NPC473623
0.5229	Remote Similarity	NPC270448
0.5225	Remote Similarity	NPC36138
0.5221	Remote Similarity	NPC11468
0.52	Remote Similarity	NPC305811
0.5192	Remote Similarity	NPC265115
0.5189	Remote Similarity	NPC275454
0.5189	Remote Similarity	NPC163242
0.5189	Remote Similarity	NPC272068
0.5175	Remote Similarity	NPC470451
0.5172	Remote Similarity	NPC146679
0.5152	Remote Similarity	NPC77672
0.5152	Remote Similarity	NPC133671
0.5152	Remote Similarity	NPC19709
0.5152	Remote Similarity	NPC135391
0.5152	Remote Similarity	NPC78263
0.5152	Remote Similarity	NPC250069
0.514	Remote Similarity	NPC293626
0.514	Remote Similarity	NPC479405
0.514	Remote Similarity	NPC605592
0.5138	Remote Similarity	NPC245452
0.5135	Remote Similarity	NPC471669
0.5133	Remote Similarity	NPC214621
0.5133	Remote Similarity	NPC34267
0.5128	Remote Similarity	NPC470716
0.5126	Remote Similarity	NPC298666
0.5126	Remote Similarity	NPC480445
0.51	Remote Similarity	NPC265530
0.5098	Remote Similarity	NPC159579
0.5098	Remote Similarity	NPC219904
0.5094	Remote Similarity	NPC139320
0.5093	Remote Similarity	NPC479404
0.5093	Remote Similarity	NPC470444
0.5083	Remote Similarity	NPC474522
0.505	Remote Similarity	NPC488080
0.505	Remote Similarity	NPC169977
0.5048	Remote Similarity	NPC172807
0.5046	Remote Similarity	NPC475366
0.5045	Remote Similarity	NPC270675
0.5045	Remote Similarity	NPC195685
0.5043	Remote Similarity	NPC470416
0.5042	Remote Similarity	NPC488739
0.5041	Remote Similarity	NPC470720

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC539691 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5686
0.1-0.2	3413
0.2-0.3	43
0.3-0.4	2
0.4-0.5	2
0.5-0.6	0
0.6-0.7	3
0.7-0.8	1
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
0.7143	Intermediate Similarity	NPD7251	Phase 2
0.6699	Remote Similarity	NPD7808	Phase 3
0.6531	Remote Similarity	NPD6797	Phase 2
0.6117	Remote Similarity	NPD7054	Phase 4

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