NPASS Compound

Natural Product: NPC30779

Natural Product ID	NPC30779
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Thalirugidine
IUPAC Name	(1S)-1-[[4-[5-[[(1S)-5-hydroxy-6,7-dimethoxy-2-methyl-3,4-dihydro-1H-isoquinolin-1-yl]methyl]-2-methoxyphenoxy]phenyl]methyl]-6,7-dimethoxy-2-methyl-3,4-dihydro-1H-isoquinolin-5-ol
Synonyms	Thalirugidine
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL504612
PubChem CID	44584027
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0002566] Isoquinolines and derivatives [CHEMONTID:0000054] Benzylisoquinolines

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 -3.4261 -1.9915 -4.8295 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5372 -1.5287 -3.8327 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.9502 -0.6695 -2.8232 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2350 -0.2119 -2.7222 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6460 0.6423 -1.7189 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7564 1.0778 -0.7558 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4583 0.6244 -0.8445 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0297 -0.2311 -1.8442 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7797 -0.7044 -1.9869 O 0 0 0 0 0 0 0 0 0 0 0 0 0.4006 -0.5372 -1.3398 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8636 0.6235 -0.7707 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0814 0.6704 -0.1370 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9032 -0.4309 -0.0364 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4180 -1.5930 -0.6180 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2187 -1.6834 -1.2535 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2148 -0.4130 0.6396 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2422 -0.0052 -0.3504 C 0 0 2 0 0 0 0 0 0 0 0 0 5.3424 -0.8685 -1.4940 N 0 0 0 0 0 0 0 0 0 0 0 0 6.0558 -2.0649 -1.1542 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0163 -0.2027 -2.5897 C 0 0 0 0 0 0 0 0 0 0 0 0 7.2408 0.5612 -2.1958 C 0 0 0 0 0 0 0 0 0 0 0 0 7.5984 0.3970 -0.7564 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6206 0.1106 0.1927 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9669 -0.0429 1.5082 C 0 0 0 0 0 0 0 0 0 0 0 0 8.2971 0.0902 1.8779 C 0 0 0 0 0 0 0 0 0 0 0 0 8.6832 -0.0606 3.1990 O 0 0 0 0 0 0 0 0 0 0 0 0 7.7142 -0.3535 4.1653 C 0 0 0 0 0 0 0 0 0 0 0 0 9.2816 0.3751 0.9470 C 0 0 0 0 0 0 0 0 0 0 0 0 8.8966 0.5234 -0.3705 C 0 0 0 0 0 0 0 0 0 0 0 0 9.9066 0.8126 -1.3052 O 0 0 0 0 0 0 0 0 0 0 0 0 10.5943 0.4970 1.3781 O 0 0 0 0 0 0 0 0 0 0 0 0 11.0155 1.8065 1.7673 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2037 2.0150 0.3332 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6988 1.2038 1.5417 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.6804 0.3699 2.0716 N 0 0 0 0 0 0 0 0 0 0 0 0 -2.9777 1.0238 3.1598 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0713 -0.9357 2.4961 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9120 -1.6509 1.4541 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0982 -0.8040 1.1985 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9809 0.5636 1.2460 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.0871 1.3886 1.0104 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.3214 0.8523 0.7252 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.4231 1.6787 0.4902 O 0 0 0 0 0 0 0 0 0 0 0 0 -9.3191 3.0769 0.5349 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.4419 -0.5208 0.6773 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.3378 -1.3283 0.9124 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.4684 -2.7059 0.8622 O 0 0 0 0 0 0 0 0 0 0 0 0 -9.6698 -1.0877 0.3936 O 0 0 0 0 0 0 0 0 0 0 0 0 -10.1125 -1.3961 -0.8994 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9025 -2.6283 -5.5530 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9964 -1.1839 -5.3060 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1762 -2.6778 -4.3343 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9442 -0.5608 -3.4905 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6698 0.9942 -1.6580 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7965 0.9707 -0.0672 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2762 1.5144 -0.8348 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4287 1.6048 0.3096 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0733 -2.4624 -0.5341 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8427 -2.5917 -1.7056 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1599 0.3650 1.4293 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4259 -1.3731 1.1498 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9696 1.0300 -0.7106 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0631 -2.0539 -1.6423 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4632 -2.9365 -1.5392 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2045 -2.1727 -0.0790 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2596 0.4277 -3.1205 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3174 -0.9863 -3.3120 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0678 1.6287 -2.4482 H 0 0 0 0 0 0 0 0 0 0 0 0 8.1334 0.2383 -2.7814 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1970 -0.2642 2.2273 H 0 0 0 0 0 0 0 0 0 0 0 0 8.2011 -0.4363 5.1662 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8891 0.3798 4.2299 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2306 -1.3505 3.9853 H 0 0 0 0 0 0 0 0 0 0 0 0 9.9913 1.8065 -1.5447 H 0 0 0 0 0 0 0 0 0 0 0 0 10.1421 2.4151 2.1225 H 0 0 0 0 0 0 0 0 0 0 0 0 11.4150 2.3780 0.8775 H 0 0 0 0 0 0 0 0 0 0 0 0 11.7334 1.7897 2.6040 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0046 2.6304 -0.0797 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3209 2.6230 0.6000 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9253 2.0057 2.3105 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1660 1.6893 2.8124 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7241 1.6524 3.7163 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5679 0.2744 3.8715 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1748 -1.5212 2.7275 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6862 -0.8795 3.4173 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3330 -1.8934 0.5494 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2171 -2.6152 1.9000 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0175 2.4738 1.0433 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.2195 3.4970 0.0043 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.4520 3.4453 -0.0619 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.2857 3.4233 1.5823 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.0597 -3.1710 0.2023 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.0139 -2.0385 -0.8232 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.4315 -0.4792 -1.4532 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.3499 -1.9438 -1.4750 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 2 0 11 12 1 0 12 13 2 0 13 14 1 0 14 15 2 0 13 16 1 0 16 17 1 0 17 18 1 0 18 19 1 0 18 20 1 0 20 21 1 0 21 22 1 0 22 23 2 0 23 24 1 0 24 25 2 0 25 26 1 0 26 27 1 0 25 28 1 0 28 29 2 0 29 30 1 0 28 31 1 0 31 32 1 0 6 33 1 0 33 34 1 0 34 35 1 0 35 36 1 0 35 37 1 0 37 38 1 0 38 39 1 0 39 40 2 0 40 41 1 0 41 42 2 0 42 43 1 0 43 44 1 0 42 45 1 0 45 46 2 0 46 47 1 0 45 48 1 0 48 49 1 0 8 3 1 0 15 10 1 0 23 17 1 0 40 34 1 0 29 22 1 0 46 39 1 0 1 50 1 0 1 51 1 0 1 52 1 0 4 53 1 0 5 54 1 0 7 55 1 0 11 56 1 0 12 57 1 0 14 58 1 0 15 59 1 0 16 60 1 0 16 61 1 0 17 62 1 6 19 63 1 0 19 64 1 0 19 65 1 0 20 66 1 0 20 67 1 0 21 68 1 0 21 69 1 0 24 70 1 0 27 71 1 0 27 72 1 0 27 73 1 0 30 74 1 0 32 75 1 0 32 76 1 0 32 77 1 0 33 78 1 0 33 79 1 0 34 80 1 1 36 81 1 0 36 82 1 0 36 83 1 0 37 84 1 0 37 85 1 0 38 86 1 0 38 87 1 0 41 88 1 0 44 89 1 0 44 90 1 0 44 91 1 0 47 92 1 0 49 93 1 0 49 94 1 0 49 95 1 0 M END

Standard InCHIKey	DITCAWDOTGUOAZ-CONSDPRKSA-N
Standard InCHI	InChI=1S/C39H46N2O8/c1-40-16-14-26-28(21-34(45-4)38(47-6)36(26)42)30(40)18-23-8-11-25(12-9-23)49-33-20-24(10-13-32(33)44-3)19-31-29-22-35(46-5)39(48-7)37(43)27(29)15-17-41(31)2/h8-13,20-22,30-31,42-43H,14-19H2,1-7H3/t30-,31-/m0/s1
SMILES	COc1ccc(cc1Oc1ccc(cc1)C[C@@H]1N(C)CCc2c1cc(OC)c(c2O)OC)C[C@@H]1N(C)CCc2c1cc(OC)c(c2O)OC

Calculated Properties

Physi-Chem Properties

Molecular Weight:	670.33	Volume:	692.439 ? Van der Waals volume.
Dense:	0.968	LogP:	3.223 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.872 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.362 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	11.0	Rigid Bonds:	34.0
TPSA:	102.32 ? Topological Polar Surface Area.	H-Bond Acceptor:	10.0
H-Bond Donor:	2.0	Rings:	6.0
Heavy Atoms:	10.0

MedChem Properties

QED Drug-Likeness Score:	0.185	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.921	Fsp³:	0.385
MCE-18:	119.222 ? 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:	Accepted	BMS Rule:	0
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.912	Fluc inhibitor:	0.173 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.614 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.818 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.002	Promiscuous compounds:	0.212

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.248	MDCK Permeability:	-4.841
Pgp-inhibitor:	0.998	Pgp-substrate:	0.265
PAMPA:	0.0 ? 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):	0.0
20% Bioavailability (F20%):	0.689	30% Bioavailability (F30%):	0.202
50% Bioavailability (F50%):	0.997

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.992	MRP1:	0.996
Plasma Protein Binding (PPB):	81.79%	Volume Distribution (VD):	-0.184
Fu:	19.244% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.995	BCRP inhibitor:	0.924
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	1.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	1.0	CYP2C9-substrate:	0.021
CYP2D6-inhibitor:	1.0	CYP2D6-substrate:	0.002
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.972	CYP2C8-inhibitor:	0.003
HLM stability:	0.971 ? 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):

5.947

Half-life (T1/2):

2.063

ADMET: Toxicity

hERG Blockers:	0.884	hERG Blockers (10um):	0.754
Human Hepatotoxicity (H-HT):	0.948	Drug-induced Liver Injury (DILI):	0.357
AMES Toxicity:	0.632	Rat Oral Acute Toxicity:	0.399
Maximum Recommended Daily Dose:	0.993	Skin Sensitization:	0.29
Carcinogencity:	0.356	Eye Corrosion:	0.0
Eye Irritation:	0.009	Respiratory Toxicity:	0.713
Drug-induced Neurotoxicity:	0.934	Ototoxicity:	0.927
Hematotoxicity:	0.12	Drug-induced Nephrotoxicity:	0.372
Genotoxicity:	0.973	RPMI-8226 Immunitoxicity:	0.141
A549 Cytotoxicity:	0.434	Hek293 Cytotoxicity:	0.937
BCF:	1.908 ? 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:	4.671 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.553 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.686 ? 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
NPO20891	Coleonema pulchellum	Species	Rutaceae	Eukaryota	n.a.	Costa Rica; Bartica, Guyana	n.a.	PMID[16124770]
NPO20891	Coleonema pulchellum	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO22044	Tamarix chinensis	Species	Tamaricaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO22044	Tamarix chinensis	Species	Tamaricaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO22044	Tamarix chinensis	Species	Tamaricaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO20891	Coleonema pulchellum	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO22044	Tamarix chinensis	Species	Tamaricaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO22044	Tamarix chinensis	Species	Tamaricaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO20320	Cryptostegia madagascariensis	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO21985	Koenigia coriaria	Species	Polygonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO20451	Vitex scabra	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO20891	Coleonema pulchellum	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO22625	Copris tripartitus	Species	Scarabaeidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO22044	Tamarix chinensis	Species	Tamaricaceae	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
Activity	2

Activity Type	# Activity
Organism	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
NPT602	Organism	Mycobacterium smegmatis	Mycobacterium smegmatis	Activity	=	1000.0	ug ml-1	DOI[10.1021/np50007a014]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	Activity	=	1000.0	ug ml-1	DOI[10.1021/np50007a014]

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 NPC30779 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	24499
0.1-0.2	22912
0.2-0.3	2157
0.3-0.4	145
0.4-0.5	67
0.5-0.6	43
0.6-0.7	23
0.7-0.8	0
0.8-0.85	0
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8507	High Similarity	NPC286119
0.7143	Intermediate Similarity	NPC247639
0.7143	Intermediate Similarity	NPC25084
0.7123	Intermediate Similarity	NPC116465
0.7	Intermediate Similarity	NPC603603
0.6456	Remote Similarity	NPC30182
0.6316	Remote Similarity	NPC311973
0.6296	Remote Similarity	NPC478963
0.6267	Remote Similarity	NPC290582
0.6267	Remote Similarity	NPC217748
0.6267	Remote Similarity	NPC182052
0.6267	Remote Similarity	NPC271013
0.6267	Remote Similarity	NPC42663
0.6267	Remote Similarity	NPC15414
0.6184	Remote Similarity	NPC279228
0.6164	Remote Similarity	NPC276890
0.6154	Remote Similarity	NPC229373
0.6145	Remote Similarity	NPC169959
0.6104	Remote Similarity	NPC239824
0.6081	Remote Similarity	NPC227060
0.6049	Remote Similarity	NPC611658
0.6027	Remote Similarity	NPC76682
0.6027	Remote Similarity	NPC10908
0.6027	Remote Similarity	NPC63646
0.6027	Remote Similarity	NPC317145
0.6027	Remote Similarity	NPC198498
0.6027	Remote Similarity	NPC115284
0.6026	Remote Similarity	NPC254441
0.5915	Remote Similarity	NPC317272
0.5915	Remote Similarity	NPC268503
0.5844	Remote Similarity	NPC73492
0.5844	Remote Similarity	NPC299990
0.5811	Remote Similarity	NPC480592
0.5789	Remote Similarity	NPC12424
0.5789	Remote Similarity	NPC129518
0.5789	Remote Similarity	NPC251580
0.573	Remote Similarity	NPC478967
0.5714	Remote Similarity	NPC603853
0.5584	Remote Similarity	NPC240841
0.5526	Remote Similarity	NPC41376
0.55	Remote Similarity	NPC475393
0.5467	Remote Similarity	NPC256012
0.5467	Remote Similarity	NPC610965
0.5443	Remote Similarity	NPC480587
0.5432	Remote Similarity	NPC185639
0.5432	Remote Similarity	NPC251735
0.5432	Remote Similarity	NPC49075
0.5432	Remote Similarity	NPC223690
0.5432	Remote Similarity	NPC9532
0.5432	Remote Similarity	NPC599951
0.5429	Remote Similarity	NPC104196
0.5312	Remote Similarity	NPC485148
0.5301	Remote Similarity	NPC181796
0.5301	Remote Similarity	NPC290005
0.5301	Remote Similarity	NPC54654
0.5301	Remote Similarity	NPC7715
0.5301	Remote Similarity	NPC328155
0.5301	Remote Similarity	NPC222661
0.5301	Remote Similarity	NPC285931
0.5294	Remote Similarity	NPC24260
0.5231	Remote Similarity	NPC213206
0.5231	Remote Similarity	NPC188163
0.5231	Remote Similarity	NPC328750
0.5227	Remote Similarity	NPC82457
0.5217	Remote Similarity	NPC317439
0.5176	Remote Similarity	NPC212237
0.5165	Remote Similarity	NPC48490
0.5116	Remote Similarity	NPC8836
0.5077	Remote Similarity	NPC314682
0.5068	Remote Similarity	NPC264850
0.5059	Remote Similarity	NPC195538

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC30779 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3704
0.1-0.2	5235
0.2-0.3	196
0.3-0.4	9
0.4-0.5	2
0.5-0.6	3
0.6-0.7	1
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
0.6027	Remote Similarity	NPD8099	Discontinued
0.5714	Remote Similarity	NPD8156	Discontinued
0.5641	Remote Similarity	NPD8095	Phase 1
0.5231	Remote Similarity	NPD4664	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