NPASS Compound

Natural Product: NPC531720

Natural Product ID	NPC531720
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(1~{R})-7-[5-[[(1~{S})-6,7-dimethoxy-2-methyl-3,4-dihydro-1~{H}-isoquinolin-1-yl]methyl]-2,3-dimethoxy-phenoxy]-1-[(3,4-dimethoxyphenyl)methyl]-5,6-dimethoxy-2-methyl-3,4-dihydro-1~{H}-isoquinoline
IUPAC Name	(1~{R})-7-[5-[[(1~{S})-6,7-dimethoxy-2-methyl-3,4-dihydro-1~{H}-isoquinolin-1-yl]methyl]-2,3-dimethoxy-phenoxy]-1-[(3,4-dimethoxyphenyl)methyl]-5,6-dimethoxy-2-methyl-3,4-dihydro-1~{H}-isoquinoline
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 105110 0 0 0 0 0 0 0 0999 V2000 11.3303 2.8545 0.6216 C 0 0 0 0 0 0 0 0 0 0 0 0 10.7713 1.6227 0.9668 O 0 0 0 0 0 0 0 0 0 0 0 0 9.4166 1.3765 1.0543 C 0 0 0 0 0 0 0 0 0 0 0 0 8.4632 2.3326 0.8069 C 0 0 0 0 0 0 0 0 0 0 0 0 7.1139 2.0659 0.9000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6748 0.7891 1.2559 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2269 0.4744 1.3650 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6389 -0.0162 0.0588 C 0 0 2 0 0 0 0 0 0 0 0 0 3.2154 -0.2906 0.2972 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3274 0.7643 0.2528 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9874 0.5466 0.4729 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0961 1.6013 0.4291 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.9337 1.5489 -0.5045 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2634 1.5737 -0.0921 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3236 1.5241 -0.9798 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7393 1.5530 -0.5152 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2205 0.1140 -0.2773 C 0 0 1 0 0 0 0 0 0 0 0 0 -6.6075 0.0811 0.1829 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.8932 0.1273 1.5580 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.2118 0.0997 1.9652 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.5582 0.1423 3.3055 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.5273 0.2154 4.2685 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.2254 0.0281 1.0348 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.5330 0.0029 1.4891 O 0 0 0 0 0 0 0 0 0 0 0 0 -11.5717 -0.0702 0.5352 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.9413 -0.0176 -0.3219 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.6330 0.0093 -0.7353 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.2593 -0.0420 -2.1826 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0806 -0.9765 -2.2687 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9646 -0.6211 -1.4651 N 0 0 0 0 0 0 0 0 0 0 0 0 -4.2645 -1.8528 -1.1054 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0048 1.4475 -2.3171 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7120 1.4189 -2.7952 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4057 1.3411 -4.1523 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.4941 1.2906 -5.0569 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6840 1.4706 -1.8731 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6199 1.4438 -2.3215 O 0 0 0 0 0 0 0 0 0 0 0 0 1.3806 2.5800 -2.6480 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5726 -0.7586 0.7374 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7783 -0.9796 0.9595 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.2971 -0.9013 2.2759 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4526 -1.8168 0.7834 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0629 -3.1195 1.0439 O 0 0 0 0 0 0 0 0 0 0 0 0 1.0580 -3.5173 2.4176 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7818 -1.5729 0.5607 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8201 -2.6326 0.5858 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8099 -2.3668 -0.4883 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3892 -1.0800 -0.4943 N 0 0 0 0 0 0 0 0 0 0 0 0 6.2033 -0.7602 -1.6116 C 0 0 0 0 0 0 0 0 0 0 0 0 7.6498 -0.1536 1.4992 C 0 0 0 0 0 0 0 0 0 0 0 0 9.0025 0.0985 1.4101 C 0 0 0 0 0 0 0 0 0 0 0 0 9.9592 -0.8787 1.6631 O 0 0 0 0 0 0 0 0 0 0 0 0 9.4992 -2.1662 2.0223 C 0 0 0 0 0 0 0 0 0 0 0 0 11.1992 3.5688 1.4770 H 0 0 0 0 0 0 0 0 0 0 0 0 10.8497 3.3035 -0.2700 H 0 0 0 0 0 0 0 0 0 0 0 0 12.4065 2.7340 0.4808 H 0 0 0 0 0 0 0 0 0 0 0 0 8.8350 3.3276 0.5293 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3867 2.8256 0.7030 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1359 -0.3569 2.1009 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6691 1.3713 1.6960 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7025 0.8531 -0.6474 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6449 1.7770 0.0479 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5019 1.6340 0.9641 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3625 1.9824 -1.3143 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8656 2.1683 0.3904 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5722 -0.2319 0.5873 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0812 0.1831 2.2647 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8287 1.0628 4.0845 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9011 -0.7143 4.1369 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.9061 0.2496 5.2976 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.4840 -0.9845 -0.0705 H 0 0 0 0 0 0 0 0 0 0 0 0 -12.5724 0.0227 1.0046 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.4867 0.7944 -0.1717 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.7326 -0.0732 -1.0382 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0911 0.9500 -2.6012 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.0725 -0.5043 -2.7837 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4742 -1.9974 -2.0110 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7529 -0.9898 -3.3300 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0661 -2.6299 -0.9401 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6245 -2.2133 -1.9264 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7388 -1.7613 -0.1370 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8041 1.4059 -3.0588 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1658 1.1868 -6.1038 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0934 2.2265 -4.9901 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1893 0.4560 -4.7606 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0035 2.9434 -3.6333 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4256 2.2267 -2.8356 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3588 3.3666 -1.8935 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2939 -0.4191 2.2878 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6182 -0.2639 2.9012 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3893 -1.8794 2.7557 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0000 -4.0541 2.6722 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2299 -4.1926 2.6459 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0152 -2.6388 3.0892 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3320 -3.6047 0.5355 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3813 -2.6219 1.5663 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6208 -3.1458 -0.3985 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3283 -2.5560 -1.4730 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9953 -1.5459 -1.7070 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6744 -0.7181 -2.5822 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7528 0.1890 -1.3966 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3018 -1.1452 1.7757 H 0 0 0 0 0 0 0 0 0 0 0 0 8.7273 -2.5261 1.3015 H 0 0 0 0 0 0 0 0 0 0 0 0 8.9554 -2.0926 3.0095 H 0 0 0 0 0 0 0 0 0 0 0 0 10.3415 -2.8960 2.0907 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 1 0 8 9 1 0 9 10 2 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 2 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 2 0 19 20 1 0 20 21 1 0 21 22 1 0 20 23 2 0 23 24 1 0 24 25 1 0 23 26 1 0 26 27 2 0 27 28 1 0 28 29 1 0 29 30 1 0 30 31 1 0 15 32 2 0 32 33 1 0 33 34 1 0 34 35 1 0 33 36 2 0 36 37 1 0 37 38 1 0 11 39 2 0 39 40 1 0 40 41 1 0 39 42 1 0 42 43 1 0 43 44 1 0 42 45 2 0 45 46 1 0 46 47 1 0 47 48 1 0 48 49 1 0 6 50 1 0 50 51 2 0 51 52 1 0 52 53 1 0 51 3 1 0 48 8 1 0 45 9 1 0 36 13 1 0 30 17 1 0 27 18 1 0 1 54 1 0 1 55 1 0 1 56 1 0 4 57 1 0 5 58 1 0 7 59 1 0 7 60 1 0 8 61 1 6 10 62 1 0 14 63 1 0 16 64 1 0 16 65 1 0 17 66 1 1 19 67 1 0 22 68 1 0 22 69 1 0 22 70 1 0 25 71 1 0 25 72 1 0 25 73 1 0 26 74 1 0 28 75 1 0 28 76 1 0 29 77 1 0 29 78 1 0 31 79 1 0 31 80 1 0 31 81 1 0 32 82 1 0 35 83 1 0 35 84 1 0 35 85 1 0 38 86 1 0 38 87 1 0 38 88 1 0 41 89 1 0 41 90 1 0 41 91 1 0 44 92 1 0 44 93 1 0 44 94 1 0 46 95 1 0 46 96 1 0 47 97 1 0 47 98 1 0 49 99 1 0 49100 1 0 49101 1 0 50102 1 0 53103 1 0 53104 1 0 53105 1 0 M END

Standard InCHIKey	QAQKPFYSONCQAR-AJQTZOPKSA-N
Standard InCHI	InChI=1S/C42H52N2O9/c1-43-15-13-27-22-35(47-5)36(48-6)23-29(27)31(43)18-26-20-37(49-7)41(51-9)38(21-26)53-39-24-30-28(40(50-8)42(39)52-10)14-16-44(2)32(30)17-25-11-12-33(45-3)34(19-25)46-4/h11-12,19-24,31-32H,13-18H2,1-10H3/t31-,32+/m0/s1
SMILES	COC1=CC=C(C[C@@H]2C3=CC(OC4=CC(C[C@H]5C6=CC(OC)=C(OC)C=C6CCN5C)=CC(OC)=C4OC)=C(OC)C(OC)=C3CCN2C)C=C1OC

Calculated Properties

Physi-Chem Properties

Molecular Weight:	728.37	Volume:	753.117 ? Van der Waals volume.
Dense:	0.967	LogP:	2.879 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.985 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.444 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	14.0	Rigid Bonds:	34.0
TPSA:	89.55 ? Topological Polar Surface Area.	H-Bond Acceptor:	11.0
H-Bond Donor:	0.0	Rings:	6.0
Heavy Atoms:	11.0

MedChem Properties

QED Drug-Likeness Score:	0.133	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.938	Fsp³:	0.429
MCE-18:	121.6 ? 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:	0.627	Fluc inhibitor:	0.123 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.595 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.548 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.002	Promiscuous compounds:	0.529

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.562	MDCK Permeability:	-4.58
Pgp-inhibitor:	0.997	Pgp-substrate:	0.209
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%):	0.56	30% Bioavailability (F30%):	0.02
50% Bioavailability (F50%):	0.985

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.991	MRP1:	0.999
Plasma Protein Binding (PPB):	59.009%	Volume Distribution (VD):	0.048
Fu:	38.548% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.951
OATP1B3 inhibitor:	0.967	BCRP inhibitor:	0.895
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	1.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.999	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	1.0	CYP2D6-substrate:	0.881
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	0.004
CYP2B6-substrate:	0.942	CYP2C8-inhibitor:	0.999
HLM stability:	0.435 ? 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):

8.89

Half-life (T1/2):

2.537

ADMET: Toxicity

hERG Blockers:	0.88	hERG Blockers (10um):	0.801
Human Hepatotoxicity (H-HT):	0.874	Drug-induced Liver Injury (DILI):	0.046
AMES Toxicity:	0.357	Rat Oral Acute Toxicity:	0.594
Maximum Recommended Daily Dose:	0.996	Skin Sensitization:	0.172
Carcinogencity:	0.482	Eye Corrosion:	0.0
Eye Irritation:	0.0	Respiratory Toxicity:	0.836
Drug-induced Neurotoxicity:	0.99	Ototoxicity:	0.866
Hematotoxicity:	0.076	Drug-induced Nephrotoxicity:	0.368
Genotoxicity:	0.919	RPMI-8226 Immunitoxicity:	0.148
A549 Cytotoxicity:	0.252	Hek293 Cytotoxicity:	0.787
BCF:	2.367 ? 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:	4.635 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.338 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.455 ? 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
NPO6299	Isopyrum thalictroides	Species	Ranunculaceae	Eukaryota	n.a.	root	n.a.	PMID[15143837]
NPO6299	Isopyrum thalictroides	Species	Ranunculaceae	Eukaryota	n.a.	rhizome	n.a.	PMID[15143837]
NPO6299	Isopyrum thalictroides	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO6299	Isopyrum thalictroides	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO6299	Isopyrum thalictroides	Species	Ranunculaceae	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 NPC531720 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	34026
0.1-0.2	14926
0.2-0.3	630
0.3-0.4	145
0.4-0.5	72
0.5-0.6	41
0.6-0.7	11
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	Natural Product ID
0.7	Intermediate Similarity	NPC213206
0.7	Intermediate Similarity	NPC188163
0.7	Intermediate Similarity	NPC328750
0.6818	Remote Similarity	NPC247639
0.6818	Remote Similarity	NPC25084
0.6316	Remote Similarity	NPC603853
0.6053	Remote Similarity	NPC227060
0.6032	Remote Similarity	NPC314682
0.6	Remote Similarity	NPC76682
0.6	Remote Similarity	NPC10908
0.6	Remote Similarity	NPC63646
0.6	Remote Similarity	NPC317145
0.6	Remote Similarity	NPC198498
0.6	Remote Similarity	NPC115284
0.5921	Remote Similarity	NPC276890
0.5867	Remote Similarity	NPC256012
0.5867	Remote Similarity	NPC610965
0.5844	Remote Similarity	NPC603603
0.5823	Remote Similarity	NPC480587
0.557	Remote Similarity	NPC12424
0.557	Remote Similarity	NPC129518
0.557	Remote Similarity	NPC251580
0.5556	Remote Similarity	NPC279228
0.5488	Remote Similarity	NPC475393
0.5488	Remote Similarity	NPC239824
0.5467	Remote Similarity	NPC317272
0.5467	Remote Similarity	NPC268503
0.5432	Remote Similarity	NPC290582
0.5432	Remote Similarity	NPC217748
0.5432	Remote Similarity	NPC73492
0.5432	Remote Similarity	NPC182052
0.5432	Remote Similarity	NPC271013
0.5432	Remote Similarity	NPC299990
0.5432	Remote Similarity	NPC42663
0.5432	Remote Similarity	NPC15414
0.5429	Remote Similarity	NPC135538
0.5429	Remote Similarity	NPC24233
0.5385	Remote Similarity	NPC480592
0.5357	Remote Similarity	NPC229373
0.5349	Remote Similarity	NPC212237
0.5301	Remote Similarity	NPC311973
0.5238	Remote Similarity	NPC116465
0.5238	Remote Similarity	NPC223690
0.5238	Remote Similarity	NPC9532
0.5233	Remote Similarity	NPC302275
0.5233	Remote Similarity	NPC195538
0.5217	Remote Similarity	NPC185838
0.5119	Remote Similarity	NPC600054
0.5119	Remote Similarity	NPC601504
0.5059	Remote Similarity	NPC185639
0.5059	Remote Similarity	NPC251735
0.5059	Remote Similarity	NPC254441
0.5059	Remote Similarity	NPC49075
0.5059	Remote Similarity	NPC599951
0.5059	Remote Similarity	NPC601503

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC531720 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4974
0.1-0.2	4007
0.2-0.3	146
0.3-0.4	15
0.4-0.5	4
0.5-0.6	2
0.6-0.7	1
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
0.7	Intermediate Similarity	NPD4664	Clinical (unspecified phase)
0.6	Remote Similarity	NPD8099	Discontinued
0.5696	Remote Similarity	NPD8156	Discontinued
0.5432	Remote Similarity	NPD8095	Phase 1

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